CN103623019A - Wettable herba andrographitis solid dispersion powder and preparation method thereof - Google Patents

Abstract

The invention relates to the technical field of veterinary medicine preparation and particularly relates to wettable herba andrographitis solid dispersion powder and a preparation method thereof. The wettable herba andrographitis solid dispersion powder is added with cyclodextrin, a carrier, a suspending agent and talcum powder on the basis of effective medicinal component of the herba andrographitis; by virtue of a reasonable medicine ratio and an advanced solid dispersion technology, the wettable herba andrographitis solid dispersion powder which is high in bioavailability, easy to uniformly disperse in water and beneficial to dosing of drinking water is provided. The wettable herba andrographitis solid dispersion powder provided by the invention is convenient to use, high in bioavailability, and has treatment effect (P is less than 0.05) remarkably superior to that of tilmicosin premix and commercially available herba andrographitis powder. The invention further provides a preparation method of the wettable herba andrographitis solid dispersion powder, wherein the method is simple in process, low in production cost and suitable for large-scale industrial production.

Description

A kind of wettability Herba Andrographis solid divides loose powder and preparation method thereof

Technical field

The present invention relates to technical field of animal remedy preparation, particularly a kind of wettability Herba Andrographis solid divides loose powder and preparation method thereof.

Background technology

Herba Andrographis Andrographis Paniculata(Burm.f.) and Nees ］ be Acanthaceae Herba Andrographis platymiscium, another name Lan Helian, Herba Andrographitis, India's grass, Andrographis paniculata(Burm.f.）Nees, Herba vallisneriae Spiralis, Rabdosia stracheyi(Benth.ex Hook.f.)Hara[Plectranthus stracheyi Benth.ex Hook.f., circular cone palpus medicinal herbs etc., its bitter in the mouth, cold in nature, return lung, stomach, large intestine, small intestine meridian, originate in India, all there is cultivation on the ground such as China south China, southwest, East China.Herba Andrographis has heat-clearing and toxic substances removing, and removing heat from blood detumescence function is joined Herba Menthae, Flos Chrysanthemi, Radix Platycodonis and used, can pharynx-clearing throat-benefiting; Join Gypsum Fibrosum, the Rhizoma Anemarrhenae, Flos Lonicerae, Fructus Forsythiae and use, can lung heat clearing eliminating fire and detoxication; Join the Radix Rehmanniae, Cortex Moutan, Folium Isatidis use, can removing pathogenic heat from blood and toxic substance from the body detumescence.Herba Andrographis cures mainly that acute bacillary dysentery, gastroenteritis, flu, epidemic encephalitis, tracheitis, pneumonia, pertussis, pulmonary tuberculosis, lung abscess, cholecystitis, hypertension, epistaxis, oropharynx swell and ache, furuncle carbuncle, burn due to hot liquid or fire and venom.

Modern study shows, the chemical composition of Herba Andrographis is mainly lactone and flavone compound.Lactone compound is mainly present in Folium Andrographis, mainly contain following kind: desoxyandrographolide (claim not only dexyandrographolide), andrographolide (claim not only andrographolide), neoandrographolide (claim not only Neoandrographolide), dehydrorographolide (but also claiming 14-Deoxy-11,12-didehydro-andrographolide), dexyandrographolide glycoside, desoxyandrographolide-19-β-D glycoside, 14-deoxidation-12-methoxyl group andrographolide, 14-deoxidation-11-oxidation andrographolide and Herba Andrographis are peaceful etc., and the lactone content of Herba Andrographis herb is in 2%-5% left and right; Flavone compound is mainly present in andrographis root, is mainly polymethoxyflavone.In addition, Herba Andrographis also contains the number of chemical compositions such as the nutrient substance such as protein, multivitamin and andnrographan, Herba Andrographis wax, phosterin, potassium chloride, sodium chloride, alkaloid (0.6%).Modern pharmacological research thinks, that Herba Andrographis has is antibacterial, antiviral, antipyretic, antiinflammatory, hepatic cholagogic, immunomodulating, anticancer, antiplatelet aggregation, contraception, adrenal cortex reinforcing function, venom and muscarinic action, anti-alcoholism and suppress the multiple pharmacologically actives such as acute promyelocytic leukemia cell growth.Research discovery, Herba Andrographis resists myocardial ischemia in addition with ischemia resisting reperfusion injury, protection vascular endothelial cell, adjusts fat, blood pressure lowering, atherosclerosis and the postoperative restenosis of prevention vascularization and improve the effects such as hemorheological property.

The clinical infectious disease such as trauma infection contamination, furuncle, carbuncle, erysipelas, upper respiratory tract infection, acute and chronic tonsillitis, acute and chronic pharyngitis, acute/chronic bronchitis, acute bacillary dysentery, acute gastroenteritis, urinary tract infection, endometritis, pelvic inflammatory disease, otitis media, periodontitis that are used for the treatment of.On veterinary clinic, Herba Andrographis single preparations of ephedrine is mainly used in preventing and treating the diseases such as poultry pneumonia, enteritis, diarrhoea, also has the immunity of enhancing, improves the aspect application such as raise benefit, and therefore, Herba Andrographis has larger using value on veterinary clinic.At present, Herba Andrographis has the dosage forms such as injection, tablet, powder, oral capsule or granule, wherein injection, powder and tablet are the common formulations on veterinary clinic, but while using, all there is limitation, the general breaking method of many employings in the existing dosage form preparation process of Herba Andrographis, make the powder of thick dispersity, often bioavailability is very low.In addition, existing dosage form is used inconvenient, and when tablet is used, dispensing inconvenience, is not suitable for a fairly large number of group support animal; When powder is used, need to pass through feedstuff administration, feedstuff administration requires medicine and feedstuff mix homogeneously, and mix homogeneously is more difficult during practical operation, easily causes animal to take the photograph dose too much poisoning or take the photograph the situation of the very few inefficacy of dose; And feedstuff administration malleable feedstuff local flavor, cause animal reload stress, thereby cause animal feed intake to decline and do not reach therapeutic effect; Injection dosage form therapeutic effect is good, but wastes time and energy, and is not suitable for large-scale farming.

In order to allow Herba Andrographis better applied aspect livestock-raising and raising pets, the novel form that develops a kind of bioavailability Herba Andrographis high, easy to use has great importance.

Summary of the invention

In view of this, the invention provides a kind of wettability Herba Andrographis solid minute loose powder, on the basis of the effective medicinal ingredient of Herba Andrographis, added cyclodextrin, carrier, suspending agent, Pulvis Talci, by rational drug ratio and advanced solid dispersion technology, provide a kind of bioavailability high, be easy in water dispersed, be beneficial to the wettability Herba Andrographis solid minute loose powder of drinking-water administration, wettability Herba Andrographis solid provided by the invention divides loose powder easy to use, bioavailability is high, the therapeutic effect of disease remarkable (P < 0.05) is better than to tilmicosin pre-mixing agent and commercially available Herba Andrographis end, the present invention also provides a kind of preparation method of wettability Herba Andrographis solid minute loose powder, and the method technique is simple, and low production cost is applicable to industrialized great production.

The invention provides a kind of wettability Herba Andrographis solid minute loose powder, the raw material that comprises following weight portion:

As preferably, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

The raw material preferred, wettability Herba Andrographis solid minute loose powder comprises following weight portion:

As preferably, Herba Andrographis also can be creat extract, and total drug effect of creat extract is identical with total drug effect of Herba Andrographis.

As preferably, cyclodextrin is DM-β-CD.

As preferably, carrier is a kind of or both the above mixture in sucrose, anhydrous glucose, sodium dihydrogen phosphate.

As preferably, suspending agent is xanthan gum.

As preferably, the raw material of wettability Herba Andrographis solid minute loose powder also comprises correctives.

As preferably, correctives is 0.6～1.8 weight portion.

In some embodiments of the invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

As preferably, correctives is a kind of or both the above mixture in sweeting agent, bitterness screening agent, bitter inhibitor; Preferred, correctives is the mixture of sweeting agent, bitterness screening agent, bitter inhibitor.

As preferably, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

As preferably, sweeting agent is a kind of or both the above mixture in aspartame, sucralose, neotame, glucide.

As preferably, bitterness screening agent is tannic acid.

As preferably, bitter inhibitor is phosphatidic acid.

As preferably, the raw material of wettability Herba Andrographis solid minute loose powder also comprises antioxidant.

As preferably, antioxidant comprises 2,6-di-tert-butyl-4-methy phenol.

As preferably, antioxidant is 0.0016～0.004 weight portion.

In some embodiments of the invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

As preferably, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

In other embodiment of the present invention, the raw material that wettability Herba Andrographis solid minute loose powder comprises following weight portion:

Wettability Herba Andrographis solid divides in loose powder the effect of each raw material as follows:

Herba Andrographis: having antibacterial, antiviral, antipyretic, antiinflammatory, hepatic cholagogic, immunomodulating, anticancer, antiplatelet aggregation, contraception, adrenal cortex reinforcing function, venom and muscarinic action, anti-alcoholism, suppress the multiple pharmacologically actives such as acute promyelocytic leukemia cell growth, is the main active of medicine.

Cyclodextrin: cyclodextrin can increase dissolubility and the dissolution velocity of the bad medicine of some water solublity in water effectively, it can also improve stability and the bioavailability of medicine, reduce bad smell or the bitterness of Herba Andrographis, and can reduce stimulation and the toxic and side effects of medicine, slow release and improve the dosage form of medicine.

Carrier: can make medicine height be dispersed in and form medicine-carrier solid dispersion in carrier mass, thereby increase dissolubility and the dissolution rate of insoluble drug, and can cover bad taste and the zest of smelling of medicine, improve bioavailability.

Pulvis Talci: there is the effect of dispersant and processing aid when amount of talc is few, when solid material is pulverized, be conducive to granule and pulverize and can keep stablizing of dispersion, and can guarantee that the medicine course of processing carries out smoothly; Amount of talc has the effect of quality improver and synergist after increasing.

Suspending agent: the suspending agents such as sodium carboxymethyl cellulose can increase the viscosity of disperse medium, thus the sedimentation velocity of microgranule or the hydrophilic of increase microgranule reduced.

Correctives: comprise sweeting agent, bitterness screening agent and bitter inhibitor; In feedstuff, add sweeting agent and can improve the feed intake of children age domestic animal, especially pig, can also improve feed conversion rate; The bitterness screening agents such as tannic acid can generate indissoluble salt with Herba Andrographis effective ingredient and be wrapped in outside drug particles, thereby play the effect of good elimination bitterness; The bitter inhibitors such as phosphatidic acid are alternative is combined with bitterness receptors, and prevention medicine contacts with taste bud, thereby plays good debitter effect.

Antioxidant: in Herba Andrographis, main medicinal ingredient andrographolide compounds is diterpenes diterpenoids lactones, character is extremely unstable, oxidizable, 2, the antioxidants such as 6-di-tert-butyl-4-methy phenol can stop the oxidation of medicine, can improve the stability of medicine, can keep safety and the effectiveness of medicine, and be beneficial to preparation and long preservation.

The present invention also provides a kind of preparation method of wettability Herba Andrographis solid minute loose powder, comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, dehydrated alcohol, carrier, 35 ℃～65 ℃ dry, then mix with Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, dehydrated alcohol, carrier, 35 ℃～65 ℃ dry, then mix with Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, dehydrated alcohol, carrier, 35 ℃～65 ℃ dry, then mix with Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, solvent is water or organic solvent.

Preferred, organic solvent is ethanol.

As preferably, bitterness screening agent is fat-soluble, water solublity or double dissolubility; Double dissolubility refers to both water solubles of bitterness screening agent, dissolves in again organic solvent.

In some embodiments of the invention, bitterness screening agent is water solublity, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, bitterness screening agent can be water solublity, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is water solublity, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, when bitterness screening agent is water solublity, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, water, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, bitterness screening agent can be water solublity, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, water, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is water solublity, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, water, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, when bitterness screening agent is fat-soluble, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, organic solvent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, bitterness screening agent is fat-soluble, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, organic solvent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is fat-soluble, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, organic solvent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, when bitterness screening agent is fat-soluble, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, bitterness screening agent is fat-soluble, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is fat-soluble, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is the dissolubility of holding concurrently, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis water extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, bitterness screening agent is the dissolubility of holding concurrently, and the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis organic solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, mix with cyclodextrin, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, add cyclodextrin, obtain mixture;

D) get antioxidant, dehydrated alcohol mixing, then mix with mixture, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, add cyclodextrin, obtain mixture;

D) get antioxidant, dehydrated alcohol mixing, then mix with mixture, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, add cyclodextrin, obtain mixture;

D) get antioxidant, dehydrated alcohol mixing, then mix with mixture, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

In step b), extracting solution also can be made creat extract through super-dry.

As preferably, wettability Herba Andrographis solid disperses powder, preparation method thereof as follows:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, dry, obtain creat extract;

D) get cyclodextrin, creat extract, dehydrated alcohol, carrier mixing, 35 ℃～65 ℃ dry, then mix with Pulvis Talci, suspending agent, pulverizes, and obtains.

In certain embodiments, it is as follows that wettability Herba Andrographis solid disperses powder, preparation method thereof:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, dry, obtain creat extract;

D) get cyclodextrin, bitterness screening agent, creat extract, dehydrated alcohol, carrier mixing, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, the preparation method of wettability Herba Andrographis solid minute loose powder comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get Herba Andrographis solvent extraction, obtain extracting solution;

C) get extracting solution and concentrate, dry, obtain creat extract;

D) get antioxidant, dehydrated alcohol mixing, then mix with cyclodextrin, bitterness screening agent, creat extract, carrier, 35 ℃～65 ℃ dry, then mix with sweeting agent, bitter inhibitor, Pulvis Talci, suspending agent, pulverizes, and obtains.

As preferably, wettability Herba Andrographis solid divides in the preparation method of loose powder, and in step b), solvent is the mixture of any one or both in water or ethanol.

As preferably, raw material also can directly adopt creat extract, total drug effect of creat extract is identical with total drug effect of Herba Andrographis, when in raw material, Herba Andrographis is replaced by the creat extract of identical effective ingredient, the creat extract that the 1g of take is equivalent to 5g Herba Andrographis is example, and wettability Herba Andrographis solid disperses powder, preparation method thereof as follows:

A) take respectively the raw material of following weight portion:

B) get creat extract, cyclodextrin, 60% ethanol mixing, obtain creat extract diluent;

C) get creat extract diluent, dehydrated alcohol, carrier mixing, 35 ℃～65 ℃ dry, then mix with Pulvis Talci, suspending agent, pulverizes, and obtains.

In some embodiments of the invention, it is as follows that wettability Herba Andrographis solid disperses powder, preparation method thereof:

A) take respectively the raw material of following weight portion:

B) get creat extract, cyclodextrin, bitter inhibitor, 60% ethanol mixing, obtain creat extract diluent;

C) get antioxidant, dehydrated alcohol mixing, add creat extract diluent, carrier, mix, 35 ℃～65 ℃ dry, then mix with bitterness screening agent, sweeting agent, Pulvis Talci, suspending agent, pulverizes, and obtains.

In other embodiment of the present invention, wettability Herba Andrographis solid disperses powder, preparation method thereof as follows:

A) take respectively the raw material of following weight portion:

B) get creat extract, cyclodextrin, 60% ethanol mixing, obtain creat extract diluent;

C) get antioxidant, dehydrated alcohol mixing, then mix with creat extract diluent, bitterness screening agent, carrier, 35 ℃～65 ℃ dry, then mix with bitter inhibitor, sweeting agent, Pulvis Talci, suspending agent, pulverizes, and obtains.

Wettability Herba Andrographis solid minute loose powder provided by the invention has significantly improved the dispersibility of the total effective ingredient of Herba Andrographis in water, it is evenly distributed in water for a long time, during clinical use, add water suspensoid, mode administration by drinking-water, is applicable to large-scale farming.Wettability Herba Andrographis solid minute loose powder can also be by being sprayed on feedstuff, the direct form administration of spice or drug administration by injection.

The invention provides a kind of wettability Herba Andrographis solid minute loose powder, the raw material that comprises following weight portion: Herba Andrographis 200～400 weight portions; Cyclodextrin 0.4～32 weight portion; Carrier 13.1～57.8 weight portions; Suspending agent 0.4～1.2 weight portion; Pulvis Talci 0.2 weight portion; Preferably, correctives is 0.6～1.8 weight portion; Preferred, correctives comprises a kind of in sweeting agent, bitterness screening agent, bitter inhibitor or mixture that both are above, and as preferably, wettability Herba Andrographis solid minute loose powder provided by the invention also comprises antioxidant, preferred, antioxidant is 0.0016～0.004 weight portion.In the present invention's formula, add suspending agent, significantly improved the dispersibility of the total effective ingredient of Herba Andrographis in water, it is evenly distributed in water for a long time, facilitate clinical in drinking-water administration; In wettability Herba Andrographis solid minute loose powder formula, add cyclodextrin, carrier, Pulvis Talci, and adopt solid dispersion technology to carry out the preparation of medicine, be beneficial to the dispersed of the total effective ingredient of Herba Andrographis, improved the bioavailability of medicine.In certain embodiments, in formula, add correctives, greatly improved the palatability of medicine, wherein bitterness screening agent and bitter inhibitor can effectively hide the bitterness of Herba Andrographis, sweeting agent can further increase the palatability of medicine, expanded the scope of application of wettability Herba Andrographis solid minute loose powder, the faunichron having a sharp sense of taste for pig etc., has luring function.

Formulation screening test shows, wettability Herba Andrographis solid minute loose powder provided by the invention can be dispersed in water, sedimentation velocity is slow, is beneficial to clinical drinking-water administration; In certain embodiments, wettability Herba Andrographis solid divides loose powder good palatability, and pig is had to luring function; In addition, wettability Herba Andrographis solid divides loose powder drug loading large, has improved the bioavailability of medicine, has reduced side effects of pharmaceutical drugs.

Hyopneumoniae clinical tests result is shown, wettability Herba Andrographis solid minute loose powder provided by the invention has good therapeutic effect to hyopneumoniae, and therapeutic effect is significantly better than tilmicosin pre-mixing agent; And easy to use; In certain embodiments, wettability Herba Andrographis solid divides loose powder good palatability, applied widely; In further embodiments, owing to adding antioxidant, medicine stability improves a lot; Because preparation process adopts solid dispersion technology, in wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.

Broiler Hakuri clinical tests result is shown, wettability Herba Andrographis solid minute loose powder provided by the invention has good therapeutic effect to broiler Hakuri, compares with commercially available Herba Andrographis end, and therapeutic effect is significantly increased, and easy to use; In further embodiments, owing to adding antioxidant, medicine stability improves a lot; In addition, because preparation process adopts solid dispersion technology, in wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.

Therefore, the invention provides a kind of be easy in water dispersed, be beneficial to drinking-water administration and the high wettability Herba Andrographis solid minute loose powder of bioavailability, compare with commercially available Herba Andrographis end with tilmicosin pre-mixing agent, wettability Herba Andrographis solid disperses treated powder effective, easy to use, in certain embodiments, owing to adding correctives in formula, the bitterness that has effectively hidden Herba Andrographis, has improved palatability of drugs, has expanded the scope of application of medicine; In further embodiments, owing to having added antioxidant in formula, medicine stability improves a lot; In addition, because preparation process adopts solid dispersion technology, in wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.The present invention also provides a kind of preparation method of wettability Herba Andrographis solid minute loose powder, and the method technique is simple, and low production cost is applicable to industrialized great production.

The specific embodiment

The invention provides a kind of wettability Herba Andrographis solid minute loose powder and preparation method thereof, those skilled in the art can use for reference content herein, suitably improve technological parameter and realize.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the artly, they are all deemed to be included in the present invention.Method of the present invention and application are described by preferred embodiment, related personnel obviously can change methods and applications herein or suitably change and combination within not departing from content of the present invention, spirit and scope, realizes and apply the technology of the present invention.

For pharmaceutical composition, supplementary product kind, consumption and auxiliary material combination etc., be the key factor of preparation, and can they be directly connected to the quality that obtain said preparation and the quality of the pharmaceutical preparations that obtains.For wettable powder of the present invention, main investigation index is dispersion and sedimentation velocity.Dispersion detects and medicine can be dropped in water, observes or stirs and observe its deployment conditions, and then judging that whether dispersion is qualified.Sedimentation velocity detects can be by " solution for oral administration, suspensoid for oral administration, Emulsion for oral administration " settling volume in < < People's Republic of China (PRC) veterinary drug allusion quotation (version in 2010) > > appendix than inspection technique requirement, wettability Herba Andrographis solid in embodiment is divided to the formula settling volume of loose powder than measuring, and then judge that whether product is qualified.

During drinking water for animals administration, the poor veterinary drug of some palatabilities is owing to having the bad taste of smelling, and can cause the animal amount of drinking of the sense of taste sensitivities such as pig to reduce and even not drink, thereby be difficult for reaching the therapeutic effect of expection.Therefore, the palatability of veterinary drug has larger impact for the curative effect of veterinary drug.The method that palatability detects: veterinary drug is converted to drinking water by quantity, drink for healthy swinery, observe the drinking-water situation of swinery, whether the palatability of evaluating medicine with this is good.

Drug loading is evaluated: by calculating the dosage of Herba Andrographis goods and the ratio of the wettability Herba Andrographis solid minute loose powder total amount of making, calculate wettability Herba Andrographis solid of the present invention and divide the drug loading of loose powder.

In the present invention, the test of animal clinical tests adopts wettability Herba Andrographis solid to divide loose powder to the test of hyopneumoniae clinical tests and the clinical tests test to broiler Hakuri.The stimulation that hyopneumoniae is subject to pathogenic microorganism or foreign body by the lung tissue of pig causes.Clinical main manifestations is: heating, and lack of appetite, cough, diminished breath sound, nasal cavity stream mucus, expired gas has corrupt abnormal smells from the patient.That Herba Andrographis has is antibacterial, the effect of antiviral, antipyretic, antiinflammatory, and hyopneumoniae is had to good therapeutic effect.In clinical trial of the present invention, respectively wettability Herba Andrographis solid minute loose powder provided by the invention and tilmicosin pre-mixing agent are applied to the treatment of hyopneumoniae, by the contrast of the two curative effect, have demonstrated outstanding advantage of the present invention.In the clinical tests test of wettability Herba Andrographis foot couple hyopneumoniae, it is as follows that drug level arranges standard: positive controls " spice concentration " is, according to < < veterinary drug allusion quotation > > regulation tilmicosin pre-mixing agent, the consumption of pig is calculated to gained; It is to calculate and obtain according to the consumption at the amount of drinking water weight ratio of pig and < < veterinary drug allusion quotation > > regulation Herba Andrographis end that test group " is converted drinking water concentration ".

White diarrhea disease is salmonellal in equal generable a kind of infectious disease of various ages by Pullorum Disease.Sick chicken clinical manifestation is: lethargy, and to bow and close order, disorderly, two wings are sagging for feather pine, loss of appetite or absolutely useless, faint, diarrhoea, arranges white, yellow, green or brown loose stool.Herba Andrographis can suppress the growth of Pullorum Disease Salmonella, therefore, the Hakuri of broiler is had to good therapeutic effect.The present invention, to respectively wettability Herba Andrographis solid minute loose powder provided by the invention and commercially available Herba Andrographis end being applied to the treatment of broiler Hakuri in broiler Hakuri clinical trial, by the contrast of the two curative effect, has demonstrated outstanding advantage of the present invention.

Formulation screening test shows, wettability Herba Andrographis solid minute loose powder provided by the invention can be dispersed in water, sedimentation velocity is slow, is beneficial to clinical drinking-water administration; In certain embodiments, wettability Herba Andrographis solid divides loose powder good palatability, and pig is had to luring function.In addition, wettability Herba Andrographis solid divides loose powder drug loading large, has improved the bioavailability of medicine, has reduced side effects of pharmaceutical drugs.

The clinical tests result of hyopneumoniae is shown, wettability Herba Andrographis solid minute loose powder provided by the invention has good therapeutic effect to hyopneumoniae; Therapeutic effect is significantly higher than tilmicosin pre-mixing agent, and easy to use, applied widely.The clinical tests result of broiler Hakuri is shown, wettability Herba Andrographis solid minute loose powder provided by the invention has good therapeutic effect to broiler Hakuri, compares with commercially available Herba Andrographis end, and therapeutic effect is significantly increased, and easy to use.Therefore, the invention provides a kind of be easy in water dispersed, be beneficial to drinking-water administration wettability Herba Andrographis solid minute loose powder; In certain embodiments, owing to adding correctives in formula, improve palatability of drugs, expanded the scope of application of medicine; In further embodiments, owing to having added antioxidant in formula, make the effective ingredient in Herba Andrographis more stable; In addition, owing to adopting solid dispersion technology, in wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.

The present invention also provides a kind of preparation method of wettability Herba Andrographis solid minute loose powder, and the method technique is simple, and low production cost is applicable to industrialized great production.

Wettability Herba Andrographis solid provided by the invention minute loose powder preparation test, wettability Herba Andrographis solid divide loose powder in hyopneumoniae and broiler Hakuri clinical trial, and raw materials used source is as follows:

Creat extract: manufacturer is the Wei Kang of Guanghan City, Sichuan plant company limited, and 100g Herba Andrographis crude drug is equivalent to creat extract 20g.

Tilmicosin pre-mixing agent: manufacturer is Chengdu Qiankun Animal Drug Industry Co., Ltd., contains tilmicosin 20g in 100g tilmicosin pre-mixing agent.

Herba Andrographis end: manufacturer is Chengdu Qiankun Animal Drug Industry Co., Ltd., contains Herba Andrographis primary crude drug 100g in 100g Herba Andrographis end.

Experimental animal: the sick pig of the hyopneumoniae of Chengdu suburbs and counties under the jurisdiction of a large city first pig farm natural occurrence; The sick chicken of the broiler Hakuri of Leshan chicken house natural occurrence.

Below in conjunction with embodiment, further set forth the present invention:

Embodiment 1 wettability Herba Andrographis solid divides the formula screening of loose powder

Screening formula as filled a prescription 1 in table 1～fill a prescription as shown in the of 6:

Table 1 wettability Herba Andrographis solid divides the preferred version of loose powder formula

Take respectively and in table 1, fill a prescription 1～raw material of each weight portion in 6 of filling a prescription, get creat extract, DM-β-CD, phosphatidic acid, add 60% ethanol and melt, make creat extract diluent;

Get 2,6-di-tert-butyl-4-methy phenol, add after 100mL～200mL anhydrous alcohol solution and mix for creat extract diluent, by a corresponding formula lower ormal weight, add sodium dihydrogen phosphate, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add tannic acid, aspartame, Pulvis Talci, xanthan gum, mix, pulverize, prepare wettability Herba Andrographis solid of the present invention and divide loose powder.

Formula 1～6 wettability Herba Andrographis solid minute the loose powder that make of filling a prescription are carried out to dispersion quality evaluation, the evaluation of settling volume specific mass, palatability quality evaluation and drug loading quality evaluation.

Dispersion quality evaluation: get each 1g of wettability Herba Andrographis solid minute loose powder by 1～6 preparations of filling a prescription of filling a prescription in table 1, drop into respectively in 1000mL drinking water, observe or stir and observe its deployment conditions, dispersion evaluation criterion is as shown in table 2:

Table 2 dispersion evaluation criterion

Settling volume specific mass is evaluated: get each 0.25g of wettability Herba Andrographis solid minute loose powder of formula 1～6 preparations of filling a prescription, be placed in respectively 50mL tool plug graduated cylinder, add water to 50mL, fill in closely, firmly jolting 1min, records respectively suspended matter height, calculated settlement volume ratio.

Computing formula:

Settling volume ratio=H/H0

Wherein, H0 is suspended matter elemental height; H is the height of standing 3 hours suspended matters.

Criterion of acceptability: settling volume ratio >=0.90.

Palatability quality evaluation: will convert drinking water by 0.25% concentration respectively by the wettability Herba Andrographis solid minute loose powder of 1～6 preparations of filling a prescription of filling a prescription in table 1, for healthy swinery, drink, observe and record swinery and drink situation, choose palatability grade, evaluation criterion is as shown in table 3.

Table 3 Palatability evaluation standard

opinion rating	evaluation criterion
		excellent	when the drinking-water of dosing is provided, swinery is induced by abnormal smells from the patient, initiatively fights for and drinks.
good	when the drinking-water of dosing is provided, swinery is drunk by daily drinking habit.
		poor	when the drinking-water of dosing is provided, swinery refusal is drunk or the amount of drinking decline relatively usually.

Drug loading quality evaluation: according to creat extract dosage and the wettability Herba Andrographis solid minute loose powder total drug loading of making, computing formula is as follows:

Result of the test is as shown in table 4:

Table 4 wettability Herba Andrographis solid disperses powder quality evaluation result

The listed evaluation index of his-and-hers watches 4 is carried out comprehensive analysis and can be obtained: by disperseing dressing sieve to select to the 1～6 wettability Herba Andrographis solids that make of filling a prescription of filling a prescription, obtained being uniformly dispersed, sedimentation velocity is slow, good palatability, wettability Herba Andrographis solid minute loose powder that drug loading is large, 1～5 wettability Herba Andrographis solid minute the loose powder that make of filling a prescription of wherein filling a prescription have all reached qualified level, take again and fill a prescription 4 as optimum.

As can be seen here, a wettability Herba Andrographis solid minute loose powder provided by the invention is uniformly dispersed, stablizes in water, can adopt the mode administration of drinking-water interpolation, greatly reduces the working strength of administration; And wettability Herba Andrographis solid divides loose powder good palatability, not only can also can be applicable to the sharp-nosed animals such as pig for quick animals that has a bad nose such as chickens, applied widely; Wettability Herba Andrographis solid minute loose powder has the effect of food calling while being applied to the sharp-nosed animals such as pig; In addition wettability Herba Andrographis solid divides loose powder drug loading large,

The bioavailability that has improved medicine, has reduced side effects of pharmaceutical drugs.

Embodiment 2 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filters, and reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug; Add while hot DM-β-CD, be stirred to dissolve, with sucrose, mix and make moistening soft material, 35 ℃ of oven dry of ventilating, add Pulvis Talci, xanthan gum, mix, and pulverize, and obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 3 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keep slight boiling condition to decoct and extract 3 times, 30min/ time, merge extractive liquid,, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, with tannic acid, anhydrous glucose, mix and make moistening soft material, 40 ℃ of oven dry of ventilating, add neotame, glucide, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 4 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filter, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, adds while hot DM-β-CD, be stirred to dissolve, add sodium dihydrogen phosphate, mix and make moistening soft material, 45 ℃ of oven dry of ventilating, add sucralose, neotame, aspartame, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 5 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keep slight boiling condition to decoct and extract 3 times, 30min/ time, merge extractive liquid,, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, adds while hot DM-β-CD, is stirred to dissolve; Get 2,6-di-tert-butyl-4-methy phenol, after dissolving with dehydrated alcohol 2000mL, be added in extracting solution, mix, with sucrose, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 6 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keeping slight boiling condition to decoct extracts 3 times, 30min/ time, merge extractive liquid, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2, 6-di-tert-butyl-4-methy phenol, after dissolving with dehydrated alcohol 2000mL, be added in extracting solution, mix, add tannic acid, anhydrous glucose, mix and make moistening soft material, 55 ℃ of oven dry of ventilating, add sucralose, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 7 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filters, and reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, adds while hot DM-β-CD, is stirred to dissolve; Get 2,6-di-tert-butyl-4-methy phenol, after dissolving with dehydrated alcohol 2000mL, be added in extracting solution, mix, add tannic acid, sodium dihydrogen phosphate, mix and make moistening soft material, 60 ℃ of oven dry of ventilating, add phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 8 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keep slight boiling condition to decoct and extract 3 times, 30min/ time, merge extractive liquid,, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, adds while hot DM-β-CD, is stirred to dissolve; Get tannic acid, sucrose, anhydrous glucose, mix and make moistening soft material, 65 ℃ of oven dry of ventilating, add Pulvis Talci, xanthan gum, mix, and pulverize, and obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 9 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filters, and reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2,6-di-tert-butyl-4-methy phenol, is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mixes, add tannic acid, anhydrous glucose, potassium dihydrogen phosphate, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 10 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keeping slight boiling condition to decoct extracts 3 times, 30min/ time, merge extractive liquid, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2, 6-di-tert-butyl-4-methy phenol is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mix, add tannic acid, sucrose, anhydrous glucose, potassium dihydrogen phosphate, mix and make moistening soft material, 45 ℃ of oven dry of ventilating, add glucide, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 11 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keeping slight boiling condition to decoct extracts 3 times, 30min/ time, merge extractive liquid, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2, 6-di-tert-butyl-4-methy phenol is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mix, add tannic acid, sucrose, mix and make moistening soft material, 40 ℃ of oven dry of ventilating, add neotame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 12 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filters, and reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2,6-di-tert-butyl-4-methy phenol, is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mixes, add tannic acid, anhydrous glucose, mix and make moistening soft material, 35 ℃ of oven dry of ventilating, add sucralose, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 13 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keep slight boiling condition to decoct and extract 3 times, 30min/ time, merge extractive liquid,, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, transfers 50 ℃ of aeration-dryings to, obtains creat extract; Get 2,6-di-tert-butyl-4-methy phenol, dehydrated alcohol 200L mixes, add DM-β-CD, tannic acid to mix, be stirred to dissolve, add creat extract, potassium dihydrogen phosphate, mix, make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 14 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keeping slight boiling condition to decoct extracts 3 times, 30min/ time, merge extractive liquid, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2, 6-di-tert-butyl-4-methy phenol is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mix, add tannic acid, sucrose, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 15 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filters, and reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get 2,6-di-tert-butyl-4-methy phenol is added in extracting solution after dissolving with dehydrated alcohol 2000mL, mixes, and adds tannic acid, anhydrous glucose, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 16 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get creat extract (being equivalent to crude drug 100kg), DM-β-CD, with 60% ethanol 10L, melt as creat extract diluent; Get 2,6-di-tert-butyl-4-methy phenol, after dissolving with dehydrated alcohol 2000mL, add in creat extract diluent, mix, add tannic acid, sodium dihydrogen phosphate, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 17 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with 40 ℃～45 ℃ heat-insulation soakings of 60% ethanol, extract 2 times, 3h/ time, 10 times of amounts, for the second time 8 times of amounts for the first time.Merge extractive liquid,, filter, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, adds while hot DM-β-CD, be stirred to dissolve, get tannic acid, anhydrous glucose, potassium dihydrogen phosphate, mix and make moistening soft material, 50 ℃ of oven dry of ventilating, add aspartame, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 18 wettability Herba Andrographis solids divide the preparation of loose powder

Formula:

Get Herba Andrographis, with sodium carbonate, adjust the aqueous alkali of pH=8, keep slight boiling condition to decoct and extract 3 times, 30min/ time, merge extractive liquid,, reduction vaporization is concentrated into every gram of concentrated solution that is equivalent to 3g crude drug, add while hot DM-β-CD, be stirred to dissolve, get tannic acid, sucrose, anhydrous glucose, potassium dihydrogen phosphate, mix and make moistening soft material, 45 ℃ of oven dry of ventilating, add glucide, phosphatidic acid, Pulvis Talci, xanthan gum, mix, pulverize, obtain wettability Herba Andrographis solid minute loose powder of the present invention.

Embodiment 19 wettability Herba Andrographis solids divide the clinical tests of loose powder to hyopneumoniae

Select the substantially suitable growing and fattening pigs of suffering from pneumonia of body weight, in same pig house, under identical raising condition, be divided at random following 3 groups:

Blank group: establish 15 of disease pigs, by daily feeding manner feedwater feed, not administration, is used in conjunction 7 days.

Positive controls: establish 16 of disease pigs, by 0.01% concentration spice, feeding for sick pig with tilmicosin pre-mixing agent, be used in conjunction 7 days.

Test group: establish 16 of disease pigs, convert drinking water by the wettability Herba Andrographis solid minute loose powder of embodiment 16 preparations by 0.13% concentration, drink for sick pig, be used in conjunction 7 days.

After 7 days, observe disease pig spirit appetite situation and make statistics, calculating cure rate, obvious effective rate, effective percentage and inefficiency, curative effect determinate standard is as shown in table 5.

Table 5 curative effect determinate standard

therapeutic effect	judge index
		recovery from illness	after medication 7 days, it is normal that spiritual appetite is recovered.
effective	after medication 7 days, spiritual appetite takes a turn for the better.
		invalid	after medication 7 days, symptom is not improved.

Computing formula:

Cure rate=recovery from illness case quantity/case sum * 100%

Obvious effective rate=effective case quantity/case sum * 100%

Effective percentage=cure rate+obvious effective rate

Inefficiency=Ineffective Cases quantity/case sum * 100%

Result of the test is as shown in table 6.

Table 6 wettability Herba Andrographis solid divides the clinical tests result of loose powder to hyopneumoniae

From the result of the test shown in table 6, medication is after 7 days, and blank group effective percentage is 0, and positive controls and test group effective percentage are 100%, shows that tilmicosin pre-mixing agent and wettability Herba Andrographis solid minute loose powder all have good curative effect to hyopneumoniae; And test group cure rate (100%) is significantly higher than the cure rate (81%) of positive controls; Repeatedly repeated trials shows, test repeatability is good.As can be seen here, wettability Herba Andrographis solid provided by the invention disperses treated powder effect to be significantly better than (P < 0.05) tilmicosin pre-mixing agent; In sum, wettability Herba Andrographis solid minute loose powder has good curative effect to hyopneumoniae, and therapeutic effect is significantly better than tilmicosin pre-mixing agent.

In process of the test, find, compare with tilmicosin pre-mixing agent, wettability Herba Andrographis solid provided by the invention divides loose powder easy to use, add water suspensoid, greatly reduce the working strength of administration; Due to the mode administration of taking drinking-water to add, wettability Herba Andrographis solid minute loose powder of the present invention does not in use affect the feed intake of disease pig.

In addition, owing to having added bitterness screening agent and bitter inhibitor in wettability Herba Andrographis solid minute loose powder formula, can effectively hide the bitterness of Herba Andrographis, sweeting agent can further increase the palatability of medicine, the scope of application that has expanded medicine, has food calling effect to sharp-nosed animals such as pigs.

In wettability Herba Andrographis solid minute loose powder, also add antioxidant, can effectively prevent the oxidation of Herba Andrographis effective ingredient andrographolide, improved the stability of medicine, guaranteed safety and the effectiveness of medicine, and be beneficial to preparation and longer-term storage.

Because medicine preparation process adopts solid dispersion technology, in gained wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high; And wettability Herba Andrographis solid divides loose powder drug loading large, improved the bioavailability of medicine, reduced side effects of pharmaceutical drugs.

The wettability Herba Andrographis solid minute the loose powder respectively embodiment of the present invention 1～15 and embodiment 17～18 being provided is applied in the clinical tests test of hyopneumoniae, test method is with embodiment 19, obtained experimental result is similar to embodiment 19 result of the tests, and the wettability Herba Andrographis solid providing in other embodiments of the invention disperses treated powder effect to be all significantly better than (P < 0.05) tilmicosin pre-mixing agent.

Comprehensive above-mentioned result of the test: the invention provides and be a kind ofly easy in water dispersedly, be beneficial to the wettability Herba Andrographis solid minute loose powder of drinking-water administration, compare with tilmicosin pre-mixing agent, wettability Herba Andrographis solid disperses treated powder effective, easy to use; In certain embodiments, owing to adding correctives in formula, improve palatability of drugs, expanded the scope of application of medicine; In further embodiments, owing to adding antioxidant in formula, improved the stability of medicine; In addition, because medicine preparation process adopts solid dispersion technology, in gained wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.Wettability Herba Andrographis solid minute loose powder provided by the invention is applicable to the more animal of kind and is applicable to the cultivation of different scales.

Embodiment 20 wettability Herba Andrographis solids divide the clinical tests of loose powder to broiler Hakuri

Select the sick chicken that suffers from broiler Hakuri of 20 ages in days, in same hen house, under identical raising condition, be divided at random following 3 groups:

Blank group: negative control group is raised by daily feeding manner, not administration.

Positive controls: by the 2g/ plumage dosage spice commercially available Herba Andrographis end (every 1 gram is equivalent to crude drug in whole 1g) of feeding, every day 2 times, be used in conjunction 3 days;

Test group: test group supplies drink by 1g/ plumage dosage after being watered by the wettability Herba Andrographis solid minute loose powder that embodiment 16 prepares (every 1 gram is equivalent to crude drug in whole 2g), every day 2 times, is used in conjunction 3 days;

Efficacy determination method: medication, after 3 days, is observed disease chicken spirit appetite situation and makes statistics, calculates cure rate, obvious effective rate, effective percentage and inefficiency, and curative effect determinate standard is as shown in table 7.

Table 7 curative effect determinate standard

therapeutic effect	judge index
		recovery from illness	after 3 days, it is normal that spiritual appetite is recovered, clinical symptom disappearance.
effective	after 3 days, spiritual appetite takes a turn for the better, clinical symptom disappearance or alleviate.
		invalid	after 3 days, symptom is not improved.

Computing formula:

Cure rate=recovery from illness case quantity/case sum * 100%

Obvious effective rate=effective case quantity/case sum * 100%

Effective percentage=cure rate+obvious effective rate

Inefficiency=Ineffective Cases quantity/case sum * 100%

Result of the test is as shown in table 8.

Table 8 wettability Herba Andrographis solid divides the clinical tests result of loose powder to broiler Hakuri

From the result of the test shown in table 8, medication is after 3 days, and blank group effective percentage is 0, and positive controls and test group effective percentage are 100%, shows that commercially available Herba Andrographis end and wettability Herba Andrographis solid minute loose powder all have good curative effect to broiler Hakuri; And test group cure rate (89%) is significantly higher than the cure rate (60%) of positive controls; Repeatedly repeated trials shows, test repeatability is good.As can be seen here, wettability Herba Andrographis solid provided by the invention disperses treated powder effect to be significantly better than (P < 0.05) commercially available Herba Andrographis end; In sum, wettability Herba Andrographis solid minute loose powder has good curative effect to broiler Hakuri, and therapeutic effect is significantly better than commercially available Herba Andrographis end.

In process of the test, find, relatively commercially available Herba Andrographis end spice administering mode, a wettability Herba Andrographis solid minute loose powder provided by the invention is offerd medicine by drinking-water, saves spice process, greatly reduces dispensing labor intensity.

In addition, owing to having added bitterness screening agent and bitter inhibitor in wettability Herba Andrographis solid minute loose powder formula, can effectively hide the bitterness of Herba Andrographis, sweeting agent can further increase the palatability of medicine, has expanded the scope of application of medicine.

In wettability Herba Andrographis solid minute loose powder, also add antioxidant, can effectively prevent the oxidation of Herba Andrographis effective ingredient andrographolide, improved the stability of medicine, guaranteed safety and the effectiveness of medicine, and be beneficial to preparation and longer-term storage.

Because medicine preparation process adopts solid dispersion technology, in gained wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.And wettability Herba Andrographis solid divides loose powder drug loading large, improved the bioavailability of medicine, reduced side effects of pharmaceutical drugs.

The wettability Herba Andrographis solid minute the loose powder respectively embodiment of the present invention 1～15 and embodiment 17～18 being provided is applied in the clinical tests test of broiler Hakuri, test method is with embodiment 20, obtained experimental result is similar to embodiment 20 result of the tests, and the wettability Herba Andrographis solid providing in other embodiments of the invention disperses treated powder effect to be all significantly better than (P < 0.05) commercially available Herba Andrographis end.

Comprehensive above-mentioned result of the test: the invention provides a kind of be easy in water dispersed, be beneficial to the wettability Herba Andrographis solid minute loose powder of drinking-water administration, compare with commercially available Herba Andrographis end, wettability Herba Andrographis solid disperses treated powder effective, easy to use, in certain embodiments, owing to adding correctives in formula, improve palatability of drugs, expanded the scope of application of medicine, in certain embodiments, owing to adding antioxidant in formula, improved the stability of medicine; In addition, because medicine preparation process adopts solid dispersion technology, in gained wettability Herba Andrographis solid minute loose powder, effective ingredient is uniformly dispersed, and bioavailability is high.Wettability Herba Andrographis solid minute loose powder provided by the invention is applicable to a greater variety of animals and is applicable to the cultivation of different scales.

Below be only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (10)

1. wettability Herba Andrographis solid divides a loose powder, it is characterized in that the raw material that it comprises following weight portion:

2. wettability Herba Andrographis solid according to claim 1 divides loose powder, it is characterized in that, described raw material also comprises correctives.

3. wettability Herba Andrographis solid according to claim 2 divides loose powder, it is characterized in that, described correctives is a kind of or both the above mixture in sweeting agent, bitterness screening agent, bitter inhibitor.

4. wettability Herba Andrographis solid according to claim 3 divides loose powder, it is characterized in that the raw material that it comprises following weight portion:

5. according to the wettability Herba Andrographis solid described in claim 1～4 any one, divide loose powder, it is characterized in that, described raw material also comprises antioxidant.

6. wettability Herba Andrographis solid according to claim 5 divides loose powder, it is characterized in that the raw material that it comprises following weight portion:

7. wettability Herba Andrographis solid divides the preparation method of loose powder as claimed in claim 1, it is characterized in that, comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get described Herba Andrographis solvent extraction, obtain extracting solution;

C) get described extracting solution and concentrate, mix with described cyclodextrin, dehydrated alcohol, described carrier, 35 ℃～65 ℃ dry, then mix with described Pulvis Talci, described suspending agent, pulverizes, and obtains.

8. wettability Herba Andrographis solid divides the preparation method of loose powder as claimed in claim 4, it is characterized in that, comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get described Herba Andrographis solvent extraction, obtain extracting solution;

C) get described extracting solution and concentrate, mix with described cyclodextrin, described bitterness screening agent, described carrier, 35 ℃～65 ℃ dry, then mix with described sweeting agent, described bitter inhibitor, described Pulvis Talci, described suspending agent, pulverizes, and obtains.

9. wettability Herba Andrographis solid divides the preparation method of loose powder as claimed in claim 6, it is characterized in that, comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get described Herba Andrographis solvent extraction, obtain extracting solution;

C) get described extracting solution and concentrate, add described cyclodextrin, obtain mixture;

D) get described antioxidant, dehydrated alcohol mixing, mix with described mixture, described bitterness screening agent, described carrier, 35 ℃～65 ℃ dry, then mix with described sweeting agent, described bitter inhibitor, described Pulvis Talci, described suspending agent again, pulverize, obtain.

10. wettability Herba Andrographis solid according to claim 1 divides the preparation method of loose powder, it is characterized in that, comprises the following steps:

A) take respectively the raw material of following weight portion:

B) get described Herba Andrographis solvent extraction, obtain extracting solution;

C) get described extracting solution and concentrate, dry, obtain creat extract;

D) get described cyclodextrin, described creat extract, dehydrated alcohol, the mixing of described carrier, 35 ℃～65 ℃ dry, then mix with described Pulvis Talci, described suspending agent, pulverizes, and obtains.