CN1195528C - Pilose antler composition and method for preparing the same - Google Patents
Pilose antler composition and method for preparing the same Download PDFInfo
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- CN1195528C CN1195528C CNB021410313A CN02141031A CN1195528C CN 1195528 C CN1195528 C CN 1195528C CN B021410313 A CNB021410313 A CN B021410313A CN 02141031 A CN02141031 A CN 02141031A CN 1195528 C CN1195528 C CN 1195528C
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Abstract
The present invention relates to a pilose antler composition and a preparing method thereof. The composition is prepared by mixing coating base materials prepared from beta-cyclodextrin, high ester, a protease inhibitor and organic solvent according to specific proportion and a pilose antler extract, wherein the weight ratio of the coating base materials to the pilose antler extract is from 1:1.5 to 1:2.7. The pilose antler composition has the advantages of good activity and stable property and maintains stable release in human bodies.
Description
Technical field
The invention relates to a kind of Cornu Cervi Pantotrichum compositions, especially refer to a kind of Cornu Cervi Pantotrichum compositions with special coating base material.The present invention also further is relevant to a kind of special Cornu Cervi Pantotrichum and extracts thing, and the Pilose Antler manufacture method.
Background technology
Contain amounts of protein in the Cornu Cervi Pantotrichum, win peptide and other polymer substances, human body is had enhancing immunity, the anti-ageing function of waiting for a long time.Oral script is the method for the most general also most convenient of this type of nutritional health food of picked-up, but can decompose through strong acid in the intestines and stomach because of oral nutriment, cause some macromolecule or protein to lose activity, and oral effectiveness is slower.Therefore, if can adopt non-oral way, and directly be sent in the blood, its active substance can complete preservation and effectiveness very fast.Non-oral way is generally Sublingual or nose film spray pattern.Mucosa has a large amount of absorption potential, drug absorption ability that tool is splendid and pharmacokinetics mechanism; And the surface area of Sublingual and nose film is bigger, and the ferment activity is less, thereby quite is fit to drug absorption.And spray pattern is quite convenient, liked by consumer.
But present employed Sublingual or nose film spray pattern also have many shortcomings, and for example its surface has a large amount of salivas or nasal mucus to flow, and can take away medicine herein, so that Cornu Cervi Pantotrichum extracts liquid is can the absorbed time very short; Because of the macromolecular compound poor permeability, be difficult for being absorbed simultaneously by Sublingual or nose film.And, general medicine do not coat base material coat under drug effect disappear very soon, for the drug effect that can continue 24 to 48 hours, developing a suitable coating base material real is necessity.
In processing procedure now, have many macromolecules to be applied to coating base material sustained release field, but most macromolecule extract liquid for Cornu Cervi Pantotrichum and is not suitable for, reason is as follows:
(1) Cornu Cervi Pantotrichum extraction liquid contains multiple macromolecular compound, it must have the extremely strong macromolecule of special elastic, absorption affinity and form a kind of microcapsule (microencapsulates) with a kind of, the time that can make this complex stay in Sublingual or nose film is elongated, to help Cornu Cervi Pantotrichum in absorption by human body.
(2) this macromolecular compound must be water insoluble, and molecular size just in time can hold other chemical compounds in Cornu Cervi Pantotrichum extraction thing and the prescription.
(3) employed macromolecule must be a pharmaceutical grade, and can not cause intoxicating phenomenon.In addition, end product must be through sterilisation step, and therefore, this chemical property that coats base material must as High Temperature High Pressure, still keep steady statue under the sterilization situation.
For increasing the complicated high molecular permeability in this coating base material and the Cornu Cervi Pantotrichum extraction liquid, need be dissolved in a kind of solvent with special water solublity and oil-soluble double effects.In addition, the active factors that Cornu Cervi Pantotrichum extracts in the liquid is degraded, also enzyme activity must be reduced to minimum for avoiding ferment; Therefore, a kind of ferment inhibitor of Cornu Cervi Pantotrichum extraction liquid that is applicable to should be added in this complex.
In addition,, describe a kind of fermentation milk prescription in 923, wherein add the heavy Pulveratum Cornu Cervi Pantotrichum of 7-15% at United States Patent (USP) 4,702; Because its Cornu Cervi Pantotrichum content is very low, thereby drug effect is very little.So, when Cornu Cervi Pantotrichum content is high, can produce the very low problem of water solublity, cause high-load Cornu Cervi Pantotrichum product to be difficult to be mixed with aqueous solution or spray form packing, the application of restriction Cornu Cervi Pantotrichum compositions in fluid product owing to contain many macromolecular compounds in the Cornu Cervi Pantotrichum.Therefore, still can't provide high-load Cornu Cervi Pantotrichum product in the market.
Moreover with regard to the Cornu Cervi Pantotrichum processing method, traditional Cornu Cervi Pantotrichum processing method is that Cornu Cervi Pantotrichum is extracted with ethanol or water (or ethanol adds water), pulverizes with freeze-drying then.This kind method is freezing Cornu Cervi Pantotrichum (the most handy liquid nitrogen) earlier.The shortcoming of this kind method can't extract with ethanol/water for many ingredients are arranged, and drug effect can't be brought into play, and this kind method is quite expensive.United States Patent (USP) 6,099,867 describe a kind of new processing method.The method is that Cornu Cervi Pantotrichum is calorified 100-120 ℃, 2 hours, and again through processes such as separation, homogenizing, filtration, mixing and lyophilizations.The shortcoming of the method is the too high and overlong time of heating-up temperature, and the effective ingredient in many Cornu Cervi Pantotrichums may produce chemical change and lose activity.
Summary of the invention
Main purpose of the present invention is to provide a kind of Cornu Cervi Pantotrichum compositions, absorbs without the intestines and stomach, and the active component in the Cornu Cervi Pantotrichum can be absorbed most effectively by human body, and discharges constantly.
Another object of the present invention is to provide a kind of manufacture method of Cornu Cervi Pantotrichum compositions, the active substance in the Cornu Cervi Pantotrichum effectively is coated in the polymer base material to form complex.
Another purpose of the present invention is to provide a kind of Cornu Cervi Pantotrichum to extract thing, by the specific additive of adding, and, can prepare the aqueous products that contains high-load Cornu Cervi Pantotrichum composition through the special handling step, and quite stable can not produce precipitation, can fully keep the stable of active substance in the Cornu Cervi Pantotrichum.
A further object of the present invention is to provide a kind of Pilose Antler manufacture method, can keep the active substance in the Cornu Cervi Pantotrichum, the pollution of isolated pathogenic bacteria or impurity, and thorough sterilizing, but also long preservation of its product that makes.
For achieving the above object, Cornu Cervi Pantotrichum provided by the invention extracts thing, makes in the mode that comprises the following step:
(a) provide the Pilose Antler that contains 70 to 90% percentage by weights, the aminoacid of 2 to 10% percentage by weights, the carbohydrate of 1 to 5% percentage by weight, the vitamin of 0.1 to 2% percentage by weight, the fatty acid of 0.5-1.5% percentage by weight, the total fatty acids of 5% following percentage by weight, and the pulverulent mixture of the mineral of 0.1 to 3% percentage by weight, percentage by weight wherein is as the deal benchmark with this pulverulent mixture;
(b) this pulverulent mixture is inserted in the homogenizer, add 70-80 ℃ of hot water, the ratio of this mixture and water is 1: 1.5 to 1: 8.0 weight ratio, forms a pigment shape mixture; And add the emulsifying agent of 0.1 to 1.5% percentage by weight, the tranquilizer of 0.1 to 1.0% percentage by weight and the additive of 0.005 to 0.2% percentage by weight, fully mix and be heated to 50-70 ℃, 10 to 20 minutes, percentage by weight wherein was as the deal benchmark with this pigment shape mixture;
(c) will insert a middling speed through the mixture that step (b) is handled heats to mix and fully mixes in the groove and be heated to 60-65 ℃, 30 minutes;
(d) will insert in the vacuum degasifer through the mixture that step (c) is handled and outgas, repeat 1 to 4 time;
(e) will insert homogenizing in the homogenizer through the mixture that step (d) is handled, treat homogenizing after, be quickly cooled to 4 ℃; And
(f) will insert in the aging tank of cold preservation stirring at low speed through the mixture that step (e) is handled,, finish the degassing and ageing process in 4 ℃ of following stirring at low speed 12 to 24 hours.
Wherein the homogenizing step of step (c) is divided into two sections pressure, and first section between 1,000 to 1, and between the 500psi, second section between 1,500 to 3, between the 000ps I; And this cooling means is high temperature moment (hight temperature short time, HTST) cooling fast.
Wherein this Pilose Antler is cryodesiccated Pilose Antler; And
This aminoacid is at least a to be to be selected from by alanine (alanine), spermine acid (arginine), asparagine (asparigine), acid, aspartic (aspartic acid), cystine (cystine), glutamine (glutamine), glutamic acid (glutamic acid), glycine (glycine), histidine (histidine), different white amino acid (isoleucine), white amino acid (leucine), from amino acid (lysine), MET (methionige), Phenylalanine (phenylalanine), proline (proline), silk amino acid (serine), Soviet Union's amino acid (threonine), tryptophan (tryptophan), Tyrosine (tyrosine), the group that forms with figured silk fabrics amino acid (valine) etc.
Wherein this fatty acid is at least a is to be selected from the group that is made up of stearic acid (stearic acid), oleic acid (oleicacid), linoleic acid (linioleic acid), lauric acid (lauric acid), sad (caprylic acid), capric acid (capric acid), the cool acid of meat pad in shoe (myristic acid), Palmic acid (palmitic acid) etc.; And
This carbohydrate is at least a to be to be selected from by starch (starch), maltose (maltose), fruit candy (fructose), sucrose (sucrose), glucose (glucose), Pyrusussuriensis candy (sorbitol), arabinose (arabinose), wooden candy (xylose), newborn candy (lactose), corn syrup (corn syrup solid), maltose cyclodextrin (maltodextrins), cyclodextrin (dextrine), the group that forms with dextrose etc.
Wherein this vitamin is at least a is to be selected from the group that is made up of vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, biotin (biotin) and pantothenic acid etc.; And
This mineral is at least a to be to be selected from the group that is made up of zinc, calcium, phosphorus, potassium, manganese, cobalt, ferrum, copper, sodium, magnesium, iodine, chlorine and fluorine.
At least a group that forms by mono fatty acid glyceride, difatty acid glyceride, Pyrusussuriensis sugar ester (Sorbitan), single-stearic acid (Monostearate), polysorbate acid anhydride fatty acid ester 60 (Polysorbate 60), polysorbate acid anhydride fatty acid ester 80 (Polysorbate 80), lecithin (Lecithin), beneficial face agent (Emplex), Kapp Lip river (Caprol), Mei Luo (Myyerol) that is selected from of this emulsifying agent wherein; This tranquilizer is at least a to be selected from by born of the same parents outer polysaccharide (Xanthan gum), hydroxy methocel (CMC), antler glue (Carageenan), U.S. rope (Methocol), Crewe element (Klucel), close the group that magnificent locust beam gum (Guar gum), locust bean gum (Locus bean gum), alginate (Alginates) are formed.
At least a group that forms by buffer reagent, chelating agen (sequestraut), antiseptic, food pigment that is selected from of this additive; Wherein, this buffer reagent is potassium phosphate and/or sodium phosphate; This sequestraut is EDTA, citric acid and/or polyphosphate; This antiseptic is potassium propionate and/or second dienoic acid potassium; This food pigment is to be selected from the group that is made up of No. 5, yellow, No. 6, yellow, No. 2, redness, No. 40, redness, beta-carotene.
Wherein the manufacture method of this Pilose Antler comprises following steps:
(a) Cornu Cervi Pantotrichum is soaked in about 80 to 90 ℃ of pure water 30 minutes, separates Cornu Cervi Pantotrichum skin and its hetero-organization;
(b) with Cornu Cervi Pantotrichum skin and its hetero-organization difference homogenizing;
(c) the homogenizing fluid filtration with this Cornu Cervi Pantotrichum skin removes the hair part;
(d) the Cornu Cervi Pantotrichum skin homogenizing fluid that this is removed hair mixes with its hetero-organization homogenizing fluid;
(e) fractionate aqueous solutions and precipitate part; And
(f) with this aqueous solution and this precipitate respectively at making powder in about 70 to 95 ℃ air-blow drying machine.
Wherein this step (f) also comprises this aqueous solution drying in stream shape bed dryer, and this precipitate is dry in mixing the backflow bed dryer.
Cornu Cervi Pantotrichum compositions provided by the invention, (β-cyclodextrin), high esters, protease inhibitor and the formed coating base material of organic solvent extract thing with Cornu Cervi Pantotrichum and mix and make by the beta-schardinger dextrin-of special ratios; Wherein the weight ratio of this coating base material and this Cornu Cervi Pantotrichum extraction thing is 1: 1.5 to 1: 2.7.
This beta-schardinger dextrin-wherein: high esters: protease presses down agent: the ratio of organic solvent is 1: 0.01: 0.02: 0.45 part heavy to 1: 0.20: 0.18: 0.55 part of weight.
Wherein this beta-schardinger dextrin-is a pharmaceutical grade; This high esters is to be got by the carboxylic acids reaction of the alcohols of 12 to 18 carbon of tool and 8 to 18 carbon of tool; This protease inhibitor is mucus protease inhibitor (Mucus proteinase inhibitot); And this organic solvent is propylene glycol (Propyleneglycol).
It is for the process sterilization and with the sterile manner package, and this package mode is packed for the atomizing that is fit to the transmission of nose film or Sublingual.
Wherein this Cornu Cervi Pantotrichum extraction thing is that the described Cornu Cervi Pantotrichum of claim 1 extracts thing.
Cornu Cervi Pantotrichum compositions provided by the invention, its preparation method comprises the following step:
(a) preparation coats base material, beta-schardinger dextrin-(cyclodextrin), high esters, protease inhibitor is mixed with special ratios with organic solvent, and should coat base material and add in the entry, stirs at a slow speed under room temperature 18 to 36 hours;
(b) add Cornu Cervi Pantotrichum and extract thing, under room temperature, stirred at a slow speed 18 to 24 hours;
(c) under 4 ℃, leave standstill 24 to 48 hours, wait to precipitate and separate out; And
(d) filter the taking-up precipitate.
It also comprises final precipitate is added 3 times of weight pure water mixing, and through sterilisation step, with the sterile manner package; This package mode is for being fit to the atomizing packing of nose film or Sublingual transmission.
The specific embodiment
For more understanding technology contents of the present invention, as follows especially exemplified by several preferred embodiment and pharmacokinetics or zooscopy description of test.
Cornu Cervi Pantotrichum compositions of the present invention comprise the formed coating base material of the beta-schardinger dextrin-with special ratios, high esters, protease inhibitor and organic solvent, and the Cornu Cervi Pantotrichum Fructus Citri grandis is got thing.It coats each components in proportions of base material and is preferably beta-schardinger dextrin-: high esters: protease inhibitor: the ratio of organic solvent is 1: 0.01: 0.02: 0.45 part heavy to 1: 0.20: 0.18: 0.55 part of weight; And the ratio of this coating base material and this Cornu Cervi Pantotrichum extraction thing is preferably 1: 1.5 to 1: 2.7 weight ratio.Employed arbitrary material is all pharmaceutical grade reagent.This high esters is preferably by the hydroxy acid class reaction of the alcohols of 12 to 18 carbon of tool and 8 to 18 carbon of tool and gets; This protease inhibitor is preferably the mucosa protease inhibitor; This organic solvent is preferably propylene glycol.
The manufacture method of this Cornu Cervi Pantotrichum compositions is as follows: the beta-schardinger dextrin-of aforementioned proportion, high esters, protease inhibitor are mixed with organic solvent, and as the material that coats base material, its preferable example that is suitable for is also as above-mentioned; Add pure water, the ratio of this mixture and pure water is preferably 1: 3 weight ratio, stirs at a slow speed under room temperature 18 to 36 hours, forms the suspension that coats base material.In this suspension, add as the Cornu Cervi Pantotrichum of above-mentioned ratio extracts thing, under room temperature,, form microcapsule with stir about at a slow speed 18 to 24 hours.This mixture left standstill 24 to 48 hours in 4 ℃, treated that precipitation generates.Above-mentioned precipitate is filtered out, and its filter method is not limit, and refilters with the clear water cleaning, so repeats repeatedly, gets final precipitate.This precipitate adds in 3 times of pure water again, and in homogenizing blender (homomixer) stir about 15-20 minute, after treating to mix fully, products therefrom was made the atomizing finished product through sterilization fully; Maybe this product spray drying powdered can be used for long preservation, add entry when needing again and make spraying reagent, package process whole process must be aseptic condition, and this package mode is preferably the atomizing packing that is fit to nose film or Sublingual transmission.
Employed Cornu Cervi Pantotrichum extracts the Cornu Cervi Pantotrichum extraction thing that thing also is a novelty in the Cornu Cervi Pantotrichum compositions of the present invention, and wherein the more traditional Cornu Cervi Pantotrichum product of the content of pilose antler active composition is high.As discussed previously, owing to contain many macromolecules in the Cornu Cervi Pantotrichum, can produce the problem that is insoluble in water when content is high, if want to add other compositions, also be easy to generate the phenomenon of oil-water separation; Therefore, the present invention is with special emulsifying mode head it off.According to this, Cornu Cervi Pantotrichum extraction thing of the present invention comprises Cornu Cervi Pantotrichum mixture and emulsifying reagent two parts.
This Cornu Cervi Pantotrichum mixture comprises the Pilose Antler of 70 to 90% percentage by weights, the aminoacid of 2 to 10% percentage by weights, the carbohydrate of 1 to 5% percentage by weight, the vitamin of 0.1 to 2% percentage by weight, and the mineral of 0.1 to 3% percentage by weight.Wherein, this each composition all mixes with flour, and this Pilose Antler is through cryodesiccated Pilose Antler.This aminoacid kind is not limit, being preferably one or more is selected from by alanine (alanine), spermine acid (arginine), asparagine (asparigine), acid, aspartic (aspartic acid), cystine (cystine), glutamine (glutamine), glutamic acid (glutamic acid), glycine (glycine), histidine (histidine), different white amino acid (isoleucine), white amino acid (leucine), from amino acid (lysine), MET (methionine), Phenylalanine (phenylalanine), proline (proline), silk amino acid (serine), Soviet Union's amino acid (threonine), tryptophan (tryptophan), Tyrosine (tyrosine) is with the group of figured silk fabrics amino acid essential amino acids such as (valine) composition.This fatty acid kind is not limit, and is preferably one or more and is selected from the group that is made up of stearic acid (stearic acid), oleic acid (oleic acid), linoleic acid (linoleic acid), lauric acid (lauric acid), sad (caprilic acid), capric acid (capric acid), myristic acid (myristicacid), Palmic acid (palmitic acid) etc.This carbohydrate kind is not limit, be preferably one or more and be selected from, wait the group of composition with D-glucose (dextrose) by starch (Starch), maltose (maltose), fruit candy (fructose), sucrose (sucrose), glucose (glucose), Pyrusussuriensis candy (sorbitol), arabinose (arabinose), wooden candy (xylose), newborn candy (lactose), corn syrup (corn syrup solid), maltose cyclodextrin (maltodextrins), cyclodextrin (dcxlrine).This vitamin kind is not limit, and is preferably to be selected from the group that is made up of vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, biotin (biotin) and pantothenic acid etc.This mineral types is not limit, and is preferably one or more and is selected from the group that is made up of zinc, calcium, phosphorus, potassium, manganese, cobalt, ferrum, copper, sodium, magnesium, iodine, chlorine and fluorine etc.
This emulsifying reagent comprises the emulsifying agent of 0.1 to 1.5% percentage by weight, 80 ℃ of pure water, the tranquilizer of 0.1 to 1.0% percentage by weight and additives of 0.005 to 0.2% percentage by weight, and wherein the ratio of this pure water and above-mentioned Cornu Cervi Pantotrichum mixture is 1.5: 1 to 8.0: 1.The mentioned emulsifier kind is not limit, and is preferably at least a group that is made up of mono fatty acid glyceride, difatty acid glyceride, Pyrusussuriensis sugar ester (Sorbitan), monostearate (Monostearate), polysorbate acid anhydride fatty acid ester 60 (Polysorbatc 60), polysorbate acid anhydride fatty acid ester 80 (Polysorbate 80), lecithin (Lecithin), beneficial face agent (Emplex), Caprol, Myyerol that is selected from.This tranquilizer kind is not limit, and is preferably at least a group that is made up of the outer polysaccharide (Xanthan gum) of born of the same parents, CMC glue, antler glue (Carageenan), Methocol, Klucel, pass China locust beam gum (Guar gum), locust bean gum (Locusbcan gum), alginate (Alginates) that is selected from.This additive types is not limit, and is preferably at least a group that is made up of buffer reagent, Scquestraut, antiseptic, food pigment that is selected from.Above-mentioned buffer reagent kind is not limit, and is preferably potassium phosphate and/or sodium phosphate etc.; This sequestraut kind is not limit, and is preferably edathamil (EDTA), citric acid and/or polyphosphate etc.; This antiseptic kind is not limit, and is preferably potassium propionate and/or second dienoic acid potassium etc.This food pigment can be artificial food coloring as No. 5, yellow, No. 6, yellow, No. 2, redness, No. 40, redness etc., and/or natural pigment such as beta-carotene etc.
Cornu Cervi Pantotrichum extracts the preparation of thing in the Cornu Cervi Pantotrichum compositions of the present invention, be that above-mentioned Cornu Cervi Pantotrichum mixture is inserted in the homogenizer, adding hot water earlier stirs, and temperature maintenance continued stir abouts after 10 minutes at 60 ℃, continuous all the other above-mentioned emulsifying reagent that add, fully mix and heating, be preferably and be heated to 50-70 ℃, and kept 10 to 20 minutes.Mixture suction one middling speed that to handle is afterwards heated to mix in the groove and is fully mixed and heating, is preferably and is heated to 60-65 ℃, 30 minutes; Now will outgas in this mixture suction vacuum degasifer, can optionally repeat this degassing step 1 to 4 times till air is sloughed.After step to be de-gassed was finished, with in motor suction one homogenizer, this homogenizer was preferably the two-part homogenizer with this mixture, divided two sections pressure to carry out homogenizing step, and first section between 1,000 to 1, and between the 500psi, second section between 1,500 to 3, between the 000psi.After treating that homogenizing is finished, can form an emulsifying mixt, should be quickly cooled to 3-6 ℃ by emulsive mixture, it is but cool fast that this cooling means is preferably HTST.At last this mixture is inserted in the aging tank of cold preservation stirring at low speed,, finish the degassing and ageing process, thoroughly remove air and make product homogenisation in 4 ℃ of following stirring at low speed 12 to 24 hours.At last this product is packaged in cold preservation in the plastic cement bottle, fresh-keeping its was about for 1 to 2 week.Above-mentioned " wearing out " process is to censure this mixture to stir and leave standstill, and slowly reaches the state of chemical equilibrium.
Extract in the thing at above-mentioned Cornu Cervi Pantotrichum, the manufacture method of this Pilose Antler comprises the following step: Cornu Cervi Pantotrichum is soaked in the proper temperature pure water, and water temperature is preferably 80 to 90 ℃, is more preferred from 85 ℃; In hot water, soak after about 30 minutes, treat Cornu Cervi Pantotrichum skin and other separate tissue.Remove the hair part afterwards with Cornu Cervi Pantotrichum skin and its hetero-organization difference homogenizing, and with the homogenizing fluid filtration of this Cornu Cervi Pantotrichum skin, the Cornu Cervi Pantotrichum skin homogenizing fluid that again this is removed hair mixes with its hetero-organization homogenizing fluid.Form a muddy shape suspension, fractionate aqueous solutions and precipitate part this moment; At last with this aqueous solution and this precipitate respectively at making powder in the air-blow drying machine.The temperature of this air-blow drying machine is set in 70 to 95 ℃, and this aqueous solution to be preferably in stream shape bed dryer dry its powder out-of-machine temperature preferable between 60-85 ℃, this moment, moisture should be less than 6% weight.One of preferable example is that this precipitate is dry in mixing the backflow bed dryer, and its powder out-of-machine temperature is between 60-85 ℃, and moisture is less than 7% weight.The dried powder that during use this aqueous solution and precipitate is formed respectively mixes use.
The preparation of embodiment 1 Cornu Cervi Pantotrichum material powder
It is long with a chainsaw freezing Cornu Cervi Pantotrichum to be sawn into 5 centimeters of every treaties, then with Cornu Cervi Pantotrichum with after the clean warm water cleaning, steep in 85 ℃ of water after about 30 minutes, skin and its hetero-organization of Cornu Cervi Pantotrichum separated.
The Cornu Cervi Pantotrichum skin places at a high speed and beat the fruit juice mixer homogenizing about 5 minutes after after the filtered through gauze, filtrate is removed the hair part through distilled water flushing.Its hetero-organization of Cornu Cervi Pantotrichum is through the same manner uniform filtration.Filter liquid-phase mixing with two afterwards.
Mixed liquor passes through homogenizing step after 5 minutes again, puts into centrifuge centrifugal (1000xg, 15 minutes), fetch water respectively solution and precipitate part.This aqueous solution in stream shape bed dryer dry 20 minutes, about 80 ℃ of powder out-of-machine temperature, moisture is less than 6% weight.This precipitate then in mixing the backflow bed dryer dry about 20 minutes, about 78 ℃ of powder out-of-machine temperature, moisture is less than 7% weight.Again above-mentioned two kinds of powder are ground to form fine powder with grater, remix is finished standby.This moment, this Pilose Antler moisture was less than 6.5% weight.
Embodiment 2 Cornu Cervi Pantotrichums extract the preparation of thing
A, each powder raw material prescription are as following table 1 (each ratio is all percentage by weight)
Table 1
| Raw material | ％(W/W) | Weight (gram) |
| Cornu Cervi Pantotrichum | 86.495 | 864.95 |
| From amino acid | 0.500 | 5.00 |
| Histidine | 0.400 | 4.00 |
| Proline | 0.800 | 8.00 |
| Tryptophan | 0.400 | 4.00 |
| Different white amino acid | 0.300 | 3.00 |
| White amino acid | 0.500 | 5.00 |
| Soviet Union's amino acid | 0.600 | 6.00 |
| MET | 0.200 | 2.00 |
| Spermine acid | 0.800 | 8.00 |
| Phenylalanine | 0.600 | 6.00 |
| Hard ester acid | 0.700 | 7.00 |
| Oleic acid | 0.800 | 8.00 |
| Linoleic acid | 0.800 | 8.00 |
| Lauric acid | 0.800 | 8.00 |
| Palmic acid | 0.900 | 9.00 |
| Corn syrup | 1.500 | 15.00 |
| The breast candy | 0.500 | 5.00 |
| Glucose | 0.500 | 5.00 |
| Cyclodextrin | 0.500 | 5.00 |
| Vitamin C | 0.500 | 5.00 |
| Calcium chloride | 0.800 | 8.00 |
| Magnesium chloride | 0.100 | 1.00 |
| Zinc chloride | 0.005 | 0.05 |
| Total amount (sample number into spectrum: AE-792) | 100.00 | 1,000.00 |
The Cornu Cervi Pantotrichum of B, adding emulsifying reagent extracts thing
The Cornu Cervi Pantotrichum of this adding emulsifying reagent extracts composition formula such as following table 2 (each ratio is all percentage by weight)
Table 2
| Raw material | ％(W/W) | Weight (Kg) |
| Sample number into spectrum AE-792 Cornu Cervi Pantotrichum extracts raw material | 69.37 | 69.37 |
| Pure water (80 ℃) | 30.0 | 30.0 |
| Lecithin | 0.08 | 0.08 |
| Mono fatty acid glyceride | 0.03 | 0.03 |
| Difatty acid glyceride | 0.01 | 0.01 |
| The sorbose monoglyceride | 0.10 | 0.10 |
| Antler glue GP-713 | 0.10 | 0.10 |
| Extracellular polysaccharide (Kelco) | 0.04 | 0.04 |
| Potassium phosphate | 0.10 | 0.10 |
| Salt | 0.15 | 0.15 |
| Beta-carotene | 0.02 | 0.02 |
(sample number into spectrum: HL-483)
Each composition of above-mentioned prescription adds in the homogenizer with following order: (1) adds 80 ℃ of pure water earlier; (2) add lecithin, mono fatty acid glyceride and difatty acid glyceride slowly, and the sorbose monoglyceride; (3) add potassium phosphate; (4) add slowly antler glue GP-713, add the outer polysaccharide (dissolving in the propylene glycol with 1: 10 ratio in advance) of born of the same parents again; (5) add beta-carotene; (6) add Cornu Cervi Pantotrichum at last and extract raw material (AE-792).
With stir about in above-mentioned each homogenizer that becomes to be placed in after 10 minutes, with these 100 kilograms of liquid, utilize the motor suction one small-sized mixing channel of heating, stir with middling speed, be heated to simultaneously 60 ℃ about 30 minutes, it is correct to guarantee each component ratio that test this solids content this moment.Be evacuated in the vacuum degassing machine (Deaerator) through motor after the heating again, behind four road samsara degassing scumming, with in this mixture suction one two-part homogenizer, carry out the emulsifying homogenizing again, first section pressure is 1,200psi, and second section pressure is 3,500psi; Emulsifying temperature is about 55 ℃.
After treating that emulsifying finishes, this liquid via motor suction one flash cooler internal cooling to 4 ℃, is left standstill in the suction one small-sized " aging tank " again, continue to remove air, keep this suspension mixed homogeneity simultaneously, and temperature is remained in 4 ℃ with stirring at low speed.
Suspension through above-mentioned steps is handled leaves standstill as for cold preservation in the bottle of having sterilized, observes its stability.After five months, find only to have 1% sample that the phenomenon of oil-water separation is arranged.And this suspension adds (sterilization packaging fully) in the oral liquid after with 1: 9 dilution proportion, and stability can reach 99% at normal temperatures, between storage life about 6 months.
Above-mentioned special emulsifying step is to get the optimization processing procedure via test of many times side.It below is the comparison of processing procedure of the present invention and other processing procedures.
Embodiment 3 Cornu Cervi Pantotrichum compositionss
Employed each chemical compound of this example is all pharmaceutical grade.Following all cpds is inserted in the rustless steel mixing channel according to the weight of following table 3:
Table 3
| Chemical compound | Weight (Kg) |
| Beta-schardinger dextrin- | 6.18 |
| Secondary butyl-3-pentyl ester | 0.916 |
| Mucus protein enzyme inhibitory enzyme | 0.124 |
| Propylene glycol | 2.78 |
| Total amount | 10.00 |
Above mixture is added 30 kilogram weight distilled water, and this moment, gross weight was 40 kilogram weights; With stir about at a slow speed 18 to 36 hours, form the suspension that coats base material.The Cornu Cervi Pantotrichum that adds 5.5 kilograms in this suspension extracts thing, with stir about at a slow speed 18 to 24 hours, forms microcapsule under room temperature.This mixture left standstill 24 to 48 hours in 4 ℃, treated that precipitation generates.Above-mentioned precipitate is gone out with filtered through gauze, and refilter, so repeat 3 times with the clear water cleaning.Can get about 18 kilograms of final precipitate this moment, and this precipitate is added in 55 kilograms of pure water, and stir about is 15 minutes in homogenizing blender (homomixer), after treating to mix fully, is heated to 212 °F with the transient heating machine, 2 minutes; After the cool quickly, in the vial of crossing with alcohol disinfecting of packing into, on this vial with the spraying generator.Package process whole process is aseptic condition.
Two, experiment
Test the enforcement of depositing of 1 Cornu Cervi Pantotrichum extraction thing
The processing procedure that Cornu Cervi Pantotrichum of the present invention extracts thing is the slightly solubility problem that is used in particular for solving the high-load Cornu Cervi Pantotrichum, and the order of each step or processing mode be its Special Significance of tool all.Therefore deposit the comparison of experiment with the product of the product in following each comparative example and the embodiment of the invention 2, each comparative example preparation method is as follows:
Comparative example 1
Employed prescription is as the prescription (HL-483) of embodiment 2, but when each composition added in the homogenizer, elder generation added Cornu Cervi Pantotrichum mixture (AE-792) in the entry, adds fatty acids such as lecithin afterwards again.
Comparative example 2
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, difference be this mixing channel of heating heat to 80 ℃ about 30 minutes.
Comparative example 3
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and difference is being omitted the vacuum outgas step.
Comparative example 4
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and first section pressure was 500psi when difference was emulsifying, and second section pressure is 2,000psi.
Comparative example 5
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step is as being same as comparative example 4, and difference pressure of first section when emulsifying is 1,000psi, and second section pressure is 2,500psi.
Comparative example 6
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, difference be to heat to 70 ℃ about 30 minutes.
Comparative example 7
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and difference is that the vacuum outgas step only carries out 2 times.
Comparative example 8
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and difference is that emulsion process is to carry out under 40 ℃.
Comparative example 9
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and difference is that emulsion process is to carry out under 65 ℃.
Comparative example 10
Employed prescription is as the prescription (HL-483) of embodiment 2, and each step also is same as embodiment 2, and difference is to omit last aging step.
Whether the foregoing description 2 and the sample of comparative example 1 to comparative example 10, observing primary production weekly has oil-water separation or the sedimentary phenomenon of macromolecule if being placed under the room temperature, observed altogether 6 months, and this outward appearance is embedded in following table 4 and the table 5:
The prepared Cornu Cervi Pantotrichum compositions of each processing procedure of table 4 is deposited experimental result (oil-water separation accounts for all percentages)
| 1st month | 2nd month | 3rd month | 4th month | 5th month | 6th month | |
| Embodiment 2 | 0 | 0 | 0 | 0 | 1 | 1 |
| Comparative example 1 | 26 | 29 | 30 | 33 | 36 | 45 |
| Comparative example 2 | 5 | 7 | 7 | 7 | 8 | 8 |
| Comparative example 3 | 17 | 20 | 26 | 26 | 28 | 32 |
| Comparative example 4 | 45 | 59 | 62 | 64 | 64 | 65 |
| Comparative example 5 | 27 | 28 | 29 | 29 | 31 | 34 |
| Comparative example 6 | 4 | 5 | 6 | 6 | 7 | 8 |
| Comparative example 7 | 11 | 14 | 21 | 21 | 23 | 24 |
| Comparative example 8 | 47 | 50 | 53 | 53 | 54 | 56 |
| Comparative example 9 | 33 | 33 | 33 | 35 | 35 | 36 |
| Comparative example 10 | 71 | 72 | 73 | 73 | 75 | 76 |
The prepared Cornu Cervi Pantotrichum compositions of each processing procedure of table 5 is deposited experimental result (macromolecular compound precipitation percentage ratio)
| 1st month | 2nd month | 3rd month | 4th month | 5th month | 6th month | |
| Embodiment 2 | 0 | 0 | 0 | 0 | 0 | 1 |
| Comparative example 1 | 62 | 62 | 62 | 62 | 63 | 63 |
| Comparative example 2 | 100 | 100 | 100 | 100 | 100 | 100 |
| Comparative example 3 | 58 | 59 | 59 | 59 | 59 | 60 |
| Comparative example 4 | 100 | 100 | 100 | 100 | 100 | 100 |
| Comparative example 5 | 95 | 96 | 96 | 96 | 96 | 96 |
| Comparative example 6 | 100 | 100 | 100 | 100 | 100 | 100 |
| Comparative example 7 | 47 | 48 | 48 | 51 | 51 | 51 |
| Comparative example 8 | 0 | 0 | 0 | 0 | 1 | 2 |
| Comparative example 9 | 0 | 0 | 0 | 1 | 2 | 3 |
| Comparative example 10 | 0 | 0 | 4 | 4 | 4 | 5 |
Can find by above-mentioned each comparative example, pressure (comparative example 4 and 5) when the number of times (comparative example 3 and 7) of the order (comparative example 1) that the Cornu Cervi Pantotrichum mixture adds, the temperature in the mixing channel of heating (comparative example 2), vacuum outgas, emulsifying, and aging step (comparative example 10), all can have influence on the oil-water separation or the deposited phenomenon of this Cornu Cervi Pantotrichum compositions, the personage who has the knack of this technology all can observe and learn by experience, this phenomenon can have influence on the absorbability and the usability of organism, and then influences its drug effect.Therefore, must just can prepare with particular process provided by the present invention and can keep the aqueous Cornu Cervi Pantotrichum compositions of high-load long-time stable, homogenizing.
Test the zoopery pattern of 2 Cornu Cervi Pantotrichums extraction thing
By the finished product (HL-483) of embodiment 2 preparations, compare relatively its influence with Cornu Cervi Pantotrichum Chinese medicine preparation commonly used for mouse.Meaning is that experimental group is a Cornu Cervi Pantotrichum product of the present invention (HL-483), and matched group is the Cornu Cervi Pantotrichum Chinese medicine preparation, and the control group is not for adding any Cornu Cervi Pantotrichum compositions.This experimental technique is as experiment A, B, C.Wherein this Cornu Cervi Pantotrichum Chinese medicine preparation is to mix Pulveratum Cornu Cervi Pantotrichum 20 grams, and Herba Violae 10 restrains, and Squama Manis 3 grams, Radix Scutellariae, Yu Quan, three do not stay row, each 4 gram of Radix Glycyrrhizae, and vine of Flos Lonicerae, Fructus Forsythiae, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Gardeniae, Rhizoma Cyperi, Radix Rhapontici be 5 grams respectively, and cook with 3 times decocting.
Adopting above-mentioned sample number into spectrum is that the Cornu Cervi Pantotrichum of HL-483 extracts thing and traditional cryodesiccated Pulveratum Cornu Cervi Pantotrichum compares experiment.
Experimental subject is for making 60 of the public Mus of the about 100 grammes per square metre albino Wistar of about 6 all body weight year.These public Mus are placed cage respectively, and the about 4-6 of every cage, with Adlibitum, a kind of casein of purification is as basic food.The Cornu Cervi Pantotrichum compositions of the sample number into spectrum HL-483 dosage with 200 milligrams is added in the every food and drink food of experimental group mouse, in addition traditional Cornu Cervi Pantotrichum Chinese medicine preparation of 200 milligrams is added in the every food and drink food of matched group mouse, the diet of control group does not then add any Cornu Cervi Pantotrichum additive.Each drinking-water of organizing mouse is all distilled water, at any time supply.Feed 6 weeks after result such as following table 6 (all data are all meansigma methods):
The body weight that table 6 is taken the mouse group of Cornu Cervi Pantotrichum compositions of the present invention and traditional Cornu Cervi Pantotrichum Chinese medicine preparation changes
| Body weight (gram)/week | The 0th week | The 1st week | The 2nd week | The 3rd week | The 4th week | The 5th week | The 6th week |
| The control group | 100.0 | 102.3 | 104.7 | 105.3 | 107.7 | 108.1 | 109 |
| HL-483 | 100.0 | 105.3 | 106.2 | 108.4 | 110.8 | 113.4 | 114.2 |
| Tradition Cornu Cervi Pantotrichum Chinese medicine preparation | 100.0 | 102.2 | 104.7 | 104.9 | 106.7 | 108.7 | 109.3 |
Can learn that by above result Cornu Cervi Pantotrichum of the present invention extracts the help growth effectiveness of thing (HL-483), comes well than control group and traditional Cornu Cervi Pantotrichum Chinese medicine preparation.And the contained Cornu Cervi Pantotrichum mixture content of sample HL-483 is 35% of sample AE-792 (embodiment 1), and its weight increase amount also is about half of experiment A, confirms that Cornu Cervi Pantotrichum mixture of the present invention has repeatability for the influence of mouse growth.
The experiment of experiment B mouse defying age
Experimental technique is with experiment A, and using dosage is all 200mg.Result such as following table 7 and table 8 (all data are all meansigma methods):
Table 7 is taken the mouse group's of Cornu Cervi Pantotrichum compositions of the present invention and traditional Cornu Cervi Pantotrichum Chinese medicine preparation the interior testis sterone content of body
| Group | Testis sterone content (pg/100 μ l blood plasma) |
| The control group | 42 |
| HL-483 (experimental example 2) | 95 |
| Tradition Cornu Cervi Pantotrichum Chinese medicine preparation | 71 |
*The higher expression defying age of testis sterone content effect significantly.
Table 8 is taken in the mouse colony of Cornu Cervi Pantotrichum compositions of the present invention and traditional Cornu Cervi Pantotrichum Chinese medicine preparation the MAO-B specific activity
| Group | The MAO-B activity | |
| Liver | Brain | |
| The control group | 5.7 | 2.4 |
| HL-483 (embodiment 2) | 2.5 | 0.5 |
| Tradition Cornu Cervi Pantotrichum Chinese medicine preparation | 4.3 | 1.3 |
*The active lower expression defying age degree of MAO-B significantly
HL-483 and control group and traditional Cornu Cervi Pantotrichum Chinese medicine preparation are compared as seen from the above table, and be more remarkable for the anti-aging effects of mouse.
The experiment of experiment C mouse anti-inflammatory
Experimental technique is with experiment B, and difference is that matched group is traditional Cornu Cervi Pantotrichum Chinese medicine preparation, and using dosage is all 200mg.Result such as following table 9 (all data are all meansigma methods)
The leukocyte number that table 9 is handled with Cornu Cervi Pantotrichum compositions of the present invention and traditional Cornu Cervi Pantotrichum Chinese medicine preparation compares
| White blood cell count/milliliter * 10 -5 | |
| The control group | 36 |
| HL-483 | 6 |
| Tradition lyophilization Pulveratum Cornu Cervi Pantotrichum | 17 |
*The leukocyte number is fewer, and expression anti-inflammatory effect better
The anti-inflammatory effect of HL-483 is better than traditional Cornu Cervi Pantotrichum Chinese medicine preparation as seen from the above table, and better more than the control group.Prove once again that in this Cornu Cervi Pantotrichum of the present invention extracts the excellent results of thing, not only on the stability of physicochemical properties, important breakthrough is arranged, more on drug effect, be better than Chinese medicine Cornu Cervi Pantotrichum folk prescription or compound recipe commonly used at present.
Test the pharmacokinetic study experiment (Pharmaco-kinetics study) of (contain and coat base material) of 3 Cornu Cervi Pantotrichum compositionss
This experiment is prescription more of the present invention and instructions of taking thereof, and the effect with traditional Cornu Cervi Pantotrichum extraction liquid instructions of taking especially compares in detail at work one aspect absorption of human body and the lasting release.It is to make powdering that traditional Cornu Cervi Pantotrichum extracts liquid, in the encapsulate, offers medicine with oral way.The present invention then extracts Cornu Cervi Pantotrichum the liquid complex and carries with bottled spray pattern.
(Insulin-like Growth factor IGF) fixes for one of most important composition and content in the Cornu Cervi Pantotrichum extraction liquid insulin like growth factor; Therefore we extract the representative of activity substance content in the thing as Cornu Cervi Pantotrichum with the content of IGF.All Cornu Cervi Pantotrichums extract liquid from a collection of raw material in the experiment, respectively organize difference with convenience.
A, test (In-vitro) in vitro determine complex and Cornu Cervi Pantotrichum to extract the ratio of thing
Extract the sol capsule with the Cornu Cervi Pantotrichum that does not coat polymer composite of the present invention and organize as control, and following table 10 each ratio preparation Cornu Cervi Pantotrichum extraction of the present invention thing complex, it also wraps in the capsule identical with the control group.
Table 10
The group Cornu Cervi Pantotrichum extracts liquid weight ratio-cyclodextrin weight ratio
The 1st group 11
The 2nd group 1 1.5
The 3rd group 1 2.0
The 4th group 1 2.7
The 5th group 1 3.5
It is that wherein IGF content is 150mg with a collection of finished product sampling that above-mentioned Cornu Cervi Pantotrichum extracts thing.IGF carries out chemistry quantitatively with IRMA (manufacturing of RADZM company).All the other each compositions are as described in the embodiment 1.
Above-mentioned Cornu Cervi Pantotrichum is extracted the thing complex insert respectively in the test tube, it contains 10 milliliters of PBS buffer solution, and continues to stir with agitating device.After 24 hours, all solution in the test tube are moved into carry out the IGF content analysis in another test tube, this laboratory sample is put into another 10 milliliters of new PBS buffer solution again.So measured once in per 24 hours, till 144 hours.The result is as shown in table 11 below:
Table 11
Time (h) IGF content (mg)
Control is organized the 1st group the 2nd group the 3rd group the 4th group the 5th group
0 150 150 150 150 150 150
24 35 75 135 129 123 98
48 12 54 114 107 109 73
72 0 17 80 81 77 28
96 0 3 56 52 53 9
120 0 0 32 27 25 0
144 0 0 4 5 2 0
By above result as can be known, the 2nd group of lasting releasing effect with the 4th group is best.
(In-vivo) Cornu Cervi Pantotrichum extracts the releasing research of thing complex in B, the human body
Below Shi Yan control group is packaged in the atomizing bottle but Cornu Cervi Pantotrichum extracts the thing complex as mentioned above, is to be sprayed onto experimenter Sublingual part during use, and the control group is then with oral way.
Extract the sol capsule with the Cornu Cervi Pantotrichum that does not coat polymer composite of the present invention and organize as control, and following table 12 each ratio preparation Cornu Cervi Pantotrichum extraction of the present invention thing complex, it also wraps in the capsule identical with the control group.
Table 12
The group Cornu Cervi Pantotrichum extracts liquid weight ratio-cyclodextrin weight ratio
The 1st group 11
The 2nd group 1 1.5
The 3rd group 1 2.0
The 4th group 1 2.7
The 5th group 1 3.5
It is that wherein HGH content is 150mg with a collection of finished product sampling that above-mentioned Cornu Cervi Pantotrichum extracts thing.HGH carries out chemistry quantitatively with IRMA (manufacturing of RADZM company).All the other each compositions are as described in the embodiment 3.
The experimenter takes the control group with oral way respectively, and the 1st group to the 5th group is offerd medicine to spray into the Sublingual mode.Every group 6 people, the men and women respectively accounts for half, and totally 28 groups participate in test.Experimenter's blood drawing in per 24 hours is once tested HGH content in it with the blood plasma extraction; 144 hours altogether.Result such as following table 13, these data are meansigma methods, except that indicating * person, all the other all have the significance,statistical of p=0.05.
Table 13
Time (h) HGH content (mg)
Control is organized the 1st group the 2nd group the 3rd group the 4th group the 5th group
0 150 150 150 150 150 150
24 23 105 127 132 130 112
48 0 83 109 115 117 87
72 0 50 81 87 89 62
96 0 17
* 52
* 59 58 24
120 0 0 29 33 37 3
144 0 0 3 5 9 0
*These groups do not reach significance,statistical (p＞0.05).
By above result as can be known, it is best to be still the 2nd group to the 4th group lasting releasing effect.Hence one can see that, and Cornu Cervi Pantotrichum extracts the optimum weight ratio of thing and coating base material between 1: 1.5 to 1: 2.7.Cornu Cervi Pantotrichum in this ratio extracts the thing complex more can reach lasting release more than traditional approach (control group) effect simultaneously.This experiment proves that more the Cornu Cervi Pantotrichum that coats through particular compounds of the present invention extracts thing, and in vivo in the test, this Cornu Cervi Pantotrichum extracts thing (is representative with HGH content) and can stay in the human body for 6 days, and its effect is remarkable, has some idea of.
From the above mentioned as can be known, the Cornu Cervi Pantotrichum compositions that the present invention is prepared is to adopt Sublingual or the spraying of nose film to absorb, and decomposes without gastric acid, can its interior contained active substance of complete preservation.In the invention with beta-schardinger dextrin-as coating base material, beta-schardinger dextrin-be a kind of flexible, absorption affinity is extremely strong, and is water insoluble, avirulence, the macromolecular compound of tool food safety characteristic; In addition, the employed in the present invention proper proportion of this macromolecule can coat Cornu Cervi Pantotrichum just and extract thing, and make microcapsule be of a size of optimization (2 to 10 microns), can be too not loose and slowly get loose, also can too closely not lose permeability, therefore the may command Cornu Cervi Pantotrichum extracts the rate of release of thing in blood, makes drug effect continue to discharge in 24 to 48 hours.In addition, for promoting the permeability that Cornu Cervi Pantotrichum extracts thing, the present invention adds water solublity and the splendid solvent-propylene glycol of oil-soluble especially, and its stability is extremely strong, and avirulence, is particularly suitable in the Cornu Cervi Pantotrichum prescription.In addition, the minority ferment in Sublingual and the bronchia mucosal, its inhibitor also is difficult for finding out.The present invention find to add high esters and the mucus protease inhibitor (10: 1 to 1: 9 weight ratios) of proper proportion through repeatedly experiment and further investigation, can have splendid inhibition effect and then an active substance in the protection Cornu Cervi Pantotrichum extraction thing; And this mixture quite stable can not cause the variation that coats base material.
Compare with known technology,, or only Cornu Cervi Pantotrichum is extracted thing and make powder or solution, absorb, all can't can completely keep the active substance in the Cornu Cervi Pantotrichum as the present invention with Sublingual or nose film no matter be employed traditionally oral; The prepared product of the present invention is more strengthened its time of staying and permeability on mucosa, increases its bioavailability, can keep the rate of release of active substance in the Cornu Cervi Pantotrichum simultaneously.
In addition, employed Cornu Cervi Pantotrichum extracts thing in this Cornu Cervi Pantotrichum compositions, by adding special emulsifying agent and tranquilizer, makes high-load Cornu Cervi Pantotrichum product reach the quality of stable homogeneous via specific emulsifying homogenizing step, keeps its drug effect simultaneously.The adding order of each raw material has particular order, can guarantee the homogenizing of final products; Control heating-up temperature simultaneously, this temperature can sterilize and promote each composition to disperse, and keeps the activity of Cornu Cervi Pantotrichum simultaneously.Another committed step then is to carry out homogenizing process with enough pressure, and the step that outgases, and prevents the foamed of product, avoids ferment or the active protein of tool in the composition to lose activity.Preparation method used in the present invention can solve in the known technology can't high-load Cornu Cervi Pantotrichum product assorted dissolubility problem, and prepare high-load Cornu Cervi Pantotrichum compositions, this product can further dilute or do various variations according to need, uses elasticity significantly to increase.
And this Cornu Cervi Pantotrichum extracts employed Pilose Antler manufacture method in thing, sterilizes simultaneously in dry run, the temperature height to 90 of drying machine ℃, and the pathogenic bacteria except that spore all can be finished extremely and removed; And end product is made moisture be lower than 6.5% heavy powder, this kind degree of drying spore all can't be grown, and therefore can reach disinfectant effect, salubrity requirement fully; Do not need additionally to carry out sterilization processing, compare, more can keep the active substance in the Cornu Cervi Pantotrichum, and more save cost of manufacture with conventional process.
Moreover, this Cornu Cervi Pantotrichum extracts thing, except having improved Cornu Cervi Pantotrichum content, also add multiple essential amino acid and fatty acid, and the people knows from experience the mineral and the vitamin of a large amount of losses, by experiment showed, that this Cornu Cervi Pantotrichum extracts thing and has more tonic effect than Cornu Cervi Pantotrichum Chinese medicine preparation or Cornu Cervi Pantotrichum itself commonly used, provide the effect of better help growth, defying age and anti-inflammatory.According to preparation method of the present invention, except the slightly solubility problem that can solve high-load Cornu Cervi Pantotrichum in the conventional art, also can make other compositions, no matter be fat-soluble or water solublity, uniform mixing mutually, reach goodish homogenizing effect and stability, and then provide Cornu Cervi Pantotrichum commonly used to extract effect that thing is beyond one's reach.
It should be noted that above-mentioned many embodiment give an example for convenience of explanation, the interest field that the present invention advocated should be as the criterion so that claim is described certainly, but not only limits to the foregoing description.
Claims (16)
1, a kind of Cornu Cervi Pantotrichum extracts thing, makes in the mode that comprises the following step:
(a) provide the pulverulent mixture of mineral of vitamin, 0.1 to 3% percentage by weight of carbohydrate, 0.1 to 2% percentage by weight of aminoacid, 1 to 5% percentage by weight of the Pilose Antler that contains 70 to 90% percentage by weights, 2 to 10% percentage by weights, and the fatty acid of surplus, wherein said percentage by weight is as the deal benchmark with this pulverulent mixture;
(b) this pulverulent mixture is inserted in the homogenizer, add 70-80 ℃ of hot water, the ratio of this mixture and water is 1: 1.5 to 1: 8.0 weight ratio, forms a pigment shape mixture; And add the emulsifying agent of 0.1 to 1.5% percentage by weight, the tranquilizer of 0.1 to 1.0% percentage by weight and the additive of 0.005 to 0.2% percentage by weight, fully mix and be heated to 50-70 ℃, 10 to 20 minutes, wherein said percentage by weight was as the deal benchmark with this pigment shape mixture;
(c) will insert a middling speed through the mixture that step (b) is handled heats to mix and fully mixes in the groove and be heated to 60-65 ℃, 30 minutes;
(d) will insert in the vacuum degasifer through the mixture that step (c) is handled and outgas, repeat 1 to 4 time;
(e) will insert homogenizing in the homogenizer through the mixture that step (d) is handled, treat homogenizing after, be quickly cooled to 4 ℃; And
(f) will insert in the aging tank of cold preservation stirring at low speed through the mixture that step (e) is handled,, finish the degassing and ageing process in 4 ℃ of following stirring at low speed 12 to 24 hours.
2, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that wherein the homogenizing step of step (c) is divided into two sections pressure, and first section between 1,000 to 1, and between the 500psi, second section between 1,500 to 3, between the 000psI; And this cooling means is to cool off fast high temperature moment.
3, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that wherein this Pilose Antler is cryodesiccated Pilose Antler; And
This aminoacid is at least a to be to be selected from by alanine, spermine acid, asparagine, acid, aspartic, cystine, glutamine, glutamic acid, glycine, histidine, different white amino acid, white amino acid, from amino acid, MET, Phenylalanine, proline, silk amino acid, Soviet Union's amino acid, tryptophan, Tyrosine, the group that forms with the figured silk fabrics amino acid.
4, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that, wherein this fatty acid is at least a is to be selected from the group that is made up of stearic acid, oleic acid, linoleic acid, lauric acid, sad, capric acid, the cool acid of meat pad in shoe, Palmic acid; And
This carbohydrate is at least a to be to be selected from by starch, maltose, fruit candy, sucrose, glucose, Pyrusussuriensis candy, arabinose, wooden candy, newborn candy, corn syrup, maltose cyclodextrin, cyclodextrin, with the group of D-glucose composition.
5, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that wherein this vitamin is at least a is to be selected from the group that is made up of vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, biotin and pantothenic acid; And
This mineral is at least a to be to be selected from the group that is made up of zinc, calcium, phosphorus, potassium, manganese, cobalt, ferrum, copper, sodium, magnesium, iodine, chlorine and fluorine.
6, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that, wherein at least a group that forms by mono fatty acid glyceride, difatty acid glyceride, Pyrusussuriensis sugar ester, single-stearic acid, polysorbate acid anhydride fatty acid ester 60, polysorbate acid anhydride fatty acid ester 80, lecithin, beneficial face agent, Kapp Lip river, U.S. Lip river that is selected from of this emulsifying agent; This tranquilizer is at least a to be selected from by the outer polysaccharide of born of the same parents, hydroxy methocel, antler glue, U.S. rope, Crewe element, close the group that magnificent locust beam gum, locust bean gum, alginate are formed.
7, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, it is characterized in that at least a group that is made up of buffer reagent, chelating agen, antiseptic, food pigment that is selected from of this additive; Wherein, this buffer reagent is potassium phosphate and/or sodium phosphate; This chelating agen is edathamil, citric acid and/or polyphosphate; This antiseptic is potassium propionate and/or second dienoic acid potassium; This food pigment is to be selected from the group that is made up of No. 5, yellow, No. 6, yellow, No. 2, redness, No. 40, redness, beta-carotene.
8, Cornu Cervi Pantotrichum as claimed in claim 1 extracts thing, and wherein the manufacture method of this Pilose Antler comprises following steps:
(a) Cornu Cervi Pantotrichum is soaked in about 80 to 90 ℃ of pure water 30 minutes, separates Cornu Cervi Pantotrichum skin and its hetero-organization;
(b) with Cornu Cervi Pantotrichum skin and its hetero-organization difference homogenizing;
(c) the homogenizing fluid filtration with this Cornu Cervi Pantotrichum skin removes the hair part;
(d) the Cornu Cervi Pantotrichum skin homogenizing fluid that this is removed hair mixes with its hetero-organization homogenizing fluid;
(e) fractionate aqueous solutions and precipitate part; And
(f) with this aqueous solution and this precipitate respectively at making powder in about 70 to 95 ℃ air-blow drying machine.
9, Cornu Cervi Pantotrichum as claimed in claim 8 extracts thing, and wherein this step (f) also comprises this aqueous solution drying in stream shape bed dryer, and this precipitate is dry in mixing the backflow bed dryer.
10, a kind of Cornu Cervi Pantotrichum compositions, its beta-schardinger dextrin-by special ratios, high esters, protease inhibitor and the formed coating base material of organic solvent extract thing with Cornu Cervi Pantotrichum and mix and make; Wherein the weight ratio of this coating base material and this Cornu Cervi Pantotrichum extraction thing is 1: 1.5 to 1: 2.7.
11, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that, wherein this beta-schardinger dextrin-: high esters: protease presses down agent: the ratio of organic solvent is 1: 0.01: 0.02: 0.45 part heavy to 1: 0.20: 0.18: 0.55 part of weight.
12, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that, wherein this beta-schardinger dextrin-is a pharmaceutical grade; This high esters is to be got by the carboxylic acids reaction of the alcohols of 12 to 18 carbon of tool and 8 to 18 carbon of tool; This protease inhibitor is the mucus protease inhibitor; And this organic solvent is a propylene glycol.
13, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that, it is for the process sterilization and with the sterile manner package, and this package mode is packed for the atomizing that is fit to the transmission of nose film or Sublingual.
14, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that, wherein this Cornu Cervi Pantotrichum extraction thing is that the described Cornu Cervi Pantotrichum of claim 1 extracts thing.
15, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that its preparation method comprises the following step:
(a) preparation coats base material, beta-schardinger dextrin-, high esters, protease inhibitor is mixed with special ratios with organic solvent, and should coat base material and add in the entry, stirs at a slow speed under room temperature 18 to 36 hours;
(b) add Cornu Cervi Pantotrichum and extract thing, under room temperature, stirred at a slow speed 18 to 24 hours;
(c) under 4 ℃, leave standstill 24 to 48 hours, wait to precipitate and separate out; And
(d) filter the taking-up precipitate.
16, Cornu Cervi Pantotrichum compositions as claimed in claim 10 is characterized in that, it also comprises final precipitate is added 3 times of weight pure water mixing, and through sterilisation step, with the sterile manner package; This package mode is for being fit to the atomizing packing of nose film or Sublingual transmission.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021410313A CN1195528C (en) | 2002-07-11 | 2002-07-11 | Pilose antler composition and method for preparing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021410313A CN1195528C (en) | 2002-07-11 | 2002-07-11 | Pilose antler composition and method for preparing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1466954A CN1466954A (en) | 2004-01-14 |
| CN1195528C true CN1195528C (en) | 2005-04-06 |
Family
ID=34147713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021410313A Expired - Fee Related CN1195528C (en) | 2002-07-11 | 2002-07-11 | Pilose antler composition and method for preparing the same |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1195528C (en) |
-
2002
- 2002-07-11 CN CNB021410313A patent/CN1195528C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1466954A (en) | 2004-01-14 |
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Granted publication date: 20050406 Termination date: 20200711 |