CN104983795B - A kind of compound for treating respiratory disease antibiotic preparation for animals - Google Patents

Abstract

A kind of compound for treating respiratory disease antibiotic preparation for animals, each component is according to the mass fraction in the preparation of 100 mass fractions are as follows: Doxycycline Hyclate 2~20, Honegsukle flower P.E 4~40, Baical Skullcap root P.E 2.5~25, surplus is glucose.Doxycycline Hyclate and Honegsukle flower P.E, Baical Skullcap root P.E in the present invention mutually act synergistically, and learn from other's strong points to offset one's weaknesses, cooperate with action, Western medicine is directed to disease symptoms and animal body function balance directly against pathogenic bacteria, Chinese medicine.Have the characteristics that treating both manifestation and root cause of disease, easy to use, good effect, drug resistance are low.

Description

A kind of compound for treating respiratory disease antibiotic preparation for animals

Technical field

The present invention relates to field of veterinary medicine preparation, especially a kind of animal-used compound preparation for treating respiratory disease.

Background technique

Porcine contagious pleuropneumonia (Porcine infectious pleuropneumonia) is by pleuropneumonia unwrapping wire Bacillus causes a kind of respiratory disease highly infectious of pig, also known as pig contagious infection pleuropneumonia.The Disease Distribution Extensively, in recent ten years fashion trend is in upward status, causes huge economic loss to intensive industrialized piggery, is acknowledged as Endanger one of the important epidemic disease of Pig Industry industry.China found this disease in 1987 for the first time, hereafter runs rampant and comes, and endangered day Become serious, becomes one of main epidemic disease of pig bacterial respiratory tract disease.

The prevention and treatment of the disease at present is using antibiotic or Chinese materia medica preparation.Antibiotic works primarily directed to pathogenic bacteria, and Not directly against respiratory symptoms such as asthma and coughs, and with long-term, a large amount of uses of antibiotic, antibacterial efficacy gradually subtracts Weak, so that its treatment cycle gradually increases, effect is more and more undesirable.And Chinese medicine can be treated fundamentally for disease, And there is the advantage for alleviating respiratory symptom, but its action is slow, the course for the treatment of is long, therefore receives certain limitation in use.

Doxycycline Hyclate also known as fortimicin, doxycycline, belong to semi-synthetic tetracycline antibiotics, are a kind of wide spectrums Antibiotic, antibacterial activity are better than terramycin and tetracycline.Doxycycline Hyclate has inhibition or killing effect to many bacteriums, right The bacterium of Doxycycline Hyclate sensitivity includes pneumococcus, streptococcus, part staphylococcus, bacillus anthracis, clostridium tetani, stick The gram-positive bacterias such as shape bacillus and Escherichia coli, pasteurella, salmonella, brucella, haemophilus, Cray primary The Gram-negative bacterias such as Salmonella and Actinobacillus mallei.Therefore Doxycycline Hyclate is widely used in veterinary clinic, is usually used in Prevent and treat pasteurellosis, brucellosis, anthrax and Escherichia coli and salmonella infection, acute respiratory infection, glanders, Strangles and porcine mycoplasmal pneumonia etc..

Silver yellow preparation is mainly made of honeysuckle, radix scutellariae, has clearing heat and detoxicating, anti-inflammatory and other effects, for treating upper breathing The diseases such as road infection, acute tonsillitis, pharyngitis.At present China veterinary drug national standard record YINHUANG ZHUSHEYE, oral liquid of honeysuckle flower and scutellaria, Silver yellow soluble powder etc. be Honegsukle flower P.E, Baical Skullcap root P.E production, it is curative for effect, be widely used in the prevention of livestock and poultry And treatment.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the defect of prior art, provide a kind of for treating respiratory tract disease The compound antibiotic preparation for animals of disease, Integrative Chinese-Western mutually learn from other's strong points to offset one's weaknesses, cooperate with action, and Western medicine is directly against pathogenic bacteria, Chinese medicine For disease symptoms and animal body function balance, have the characteristics that treating both manifestation and root cause of disease, easy to use, good effect, drug resistance are low.

Technical problem of the present invention is solved with following technical proposals:

A kind of compound for treating respiratory disease antibiotic preparation for animals, each component is pressed in the preparation of 100 mass fractions Mass fraction is calculated as:

Doxycycline Hyclate 2~20,

Honegsukle flower P.E 4~40,

Baical Skullcap root P.E 2.5~25

Glucose surplus.

It is above-mentioned for treating the compound antibiotic preparation for animals of respiratory disease, each component is pressed in the preparation of 100 mass fractions Mass fraction is calculated as:

Doxycycline Hyclate 10,

Honegsukle flower P.E 20,

Baical Skullcap root P.E 12.5,

Glucose surplus.

A kind of compound antibiotic preparation for animals being used to treat respiratory disease as described above is used for preparation treatment pig and passes The antibiotic preparation of metachromia pleuropneumonia.

A method of the above-mentioned compound antibiotic preparation for animals for being used to treat respiratory disease is prepared, is walked by preparation by following It is rapid to carry out:

A, Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and glucose are weighed by formula；

B, the above component crushed respectively, cross 24 meshes；

C, by Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and the appropriate glucose after sieving in mixing machine Middle premix 15 minutes, the glucose for adding surplus mixes 30 minutes, up to product after mixing.

Doxycycline Hyclate is different from the mechanism of action of honeysuckle, radix scutellariae, and Doxycycline Hyclate is quick bacteriostatic, to leather The various pathogenic bacteria such as Lan Shi positive bacteria, Gram-negative bacteria all have significant ground inhibitory or killing effect.It is golden in traditional Chinese medicine ingredients silver yellow preparation Honeysuckle flower for reducing fever, detoxicating, light clear table are main ingredient, are aided with radix scutellariae heat-clearing and damp-drying drug, purging fire for removing toxin, two medicines share rise altogether it is clearing heat and detoxicating, thoroughly The function of table eliminating evil.Honeysuckle and radix scutellariae all have clearing heat and detoxicating, anti-inflammatory and other effects, has a broad antifungal spectrum, to a variety of gram-positive bacterias It is all had a strong inhibitory effect with negative bacterium, while there is relaxation effect to disease respiratory symptom.Since honeysuckle has solution The effects of hot and anti-inflammatory, can inhibit inflammatory to ooze out, and can inhibit inflammatory hyperplasia, and can promote the phagocytosis of leucocyte, therefore The hydrops in lung and thoracic cavity can be effectively reduced, the symptoms such as stream nose liquid, expiratory dyspnea are alleviated.Radix scutellariae also has antifungic action, resists Bacterium spectrum is wide.

Doxycycline Hyclate and honeysuckle, radix scutellariae, which share, plays synergistic effect, enhances antibacterial effect, and be not likely to produce drug resistance Property.Three, which shares, in clinical use enhances to actinobacillus pleuropneumoniae antibacterial effect, can quickly kill pathogen, The effectively control state of an illness, shortens treatment course.The pharmaceutical preparation is 100% for the effective percentage for treating porcine contagious pleuropneumonia, Raising (Doxycycline Hyclate group significant in efficacy compared with Doxycycline Hyclate is treated is used alone up to 95% or more, with using in cure rate Effective percentage be 90%, cure rate 70%).

The dosage form of compound medicine of the present invention is soluble powder, and soluble powder refers to drug and suitable auxiliary material through powder Water-soluble dry powdered preparation that is broken, being uniformly mixed, is exclusively used in drinking water administration.Relative to other tablets, injection The dosage forms such as agent, easy to use, large-scale groups medication suitable for large-scale plant that raises easy using soluble powder dosing techniques.

Specific embodiment

Below with reference to embodiment, invention is further described in detail.

The present invention is the compound preparation of the composition containing Doxycycline Hyclate, Honegsukle flower P.E and Baical Skullcap root P.E, Each component is matched by following mass fraction:

2~20g of Doxycycline Hyclate,

4~40g of Honegsukle flower P.E,

2.5~25g of Baical Skullcap root P.E

Glucose adds to 100g.

Preferred compound medicament composition are as follows: contain in every 100g compound medicine:

Doxycycline Hyclate 10g,

Honegsukle flower P.E 20g,

Baical Skullcap root P.E 12.5g,

Glucose adds to 100g.

Corrigent can also be contained in compound medicine, the corrigent is essence.

Compound medicine is administered in the form of soluble powder.

Preparation method of the invention is by Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and auxiliary material glucose It after pulverizing and sieving, is mixed thoroughly, preparation method is simple.

It is preferred that being prepared using following steps:

A, Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and glucose are weighed by prescription；

B, the above component be crushed into 24 meshes respectively；

C, by Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and the appropriate glucose after sieving, (glucose adds Enter the one third or so of amount) it is premixed 15 minutes in mixing machine, the glucose that surplus is added mixes 30 minutes, after mixing i.e. ?.

Embodiment 1

The content of each component in every 100g drug are as follows:

Doxycycline Hyclate 10g,

Honegsukle flower P.E 20g,

Baical Skullcap root P.E 12.5g,

Glucose adds to 100g.

Preparation method:

Bulk pharmaceutical chemicals Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and glucose are smashed it through into 24 meshes, pressed Prescription requirements weigh Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E, and 25g glucose is added and premixes in mixing machine 15 minutes, the glucose for adding surplus mixed 30 minutes, up to animal compound pharmaceutical preparation of the invention after mixing.

Embodiment 2

The content of each component in every 100g drug:

Doxycycline Hyclate 5g,

Honegsukle flower P.E 10g,

Baical Skullcap root P.E 6.25g,

Glucose adds to 100g.

The preparation method that the preparation method is the same as that of Example 1.

Embodiment 3

The content of each component in every 100g drug:

Doxycycline Hyclate 15g,

Honegsukle flower P.E 30g,

Baical Skullcap root P.E 18.75g,

Glucose adds to 100g.

The preparation method that the preparation method is the same as that of Example 1.

Randomized controlled treatment example

1, test medicine is the soluble powder prepared according to embodiment 1；Control drug is that 10% Doxycycline Hyclate is solvable Property pulvis.

2, select that the state of an illness, the course of disease be similar, frank 100 sick pigs carry out clinical trial

In clinical case, the main clinic symptoms of sick pig are spiritual loss of appetite, asthma and cough etc., and severe cases stream is red Acute death occurs for color, rust nose liquid.Dissect death and severe sick pig, it is seen that lesion mainly has in thoracic cavity, lungs and pleura Large area lesion, consolidation occurs for lung, or even sticks together；Thoracic cavity volume hydrops and Fibrin exudation object；Pericardium outer fiber Albumen exudative inflammation is serious, and without obvious inflammation in pericardium, abdominal cavity does not have obvious abnormality.Acquire lung and pleural effusion disease Material is cultivated through TSA culture medium (tryptose soya agar), minimum bacterium colony occurs, is that Gram-negative is small through smear staining microscopy Coccobacillus, PCR detect the 16S rRNA gene of separation of bacterial, obtain expected actinobacillus pleuropneumoniae 442bp big or small slice Section.Complex clinical symptom, dissect and laboratory detection result make a definite diagnosis two pig farms successively happens is that actinobacillus pleuropneumoniae Disease.

Successively 5 groups, every group 20 are randomly divided into from two pig farms by 100 sick pigs.Wherein I, II, III group are test group, Low dosage (5mg/kg.bw.d), middle dosage (10mg/kg.bw.d), high dose (20mg/kg.bw.d) are given by drinking-water respectively According to embodiment 1 prepare soluble powder, wherein mg/kg.bw.d be every kg body weight per day need to be to the milligram number of drug. IV group is control drug group, gives doxycycline hydrochloride soluble powder by 20mg/kg.bw.d dosage；V group is not medication group, is given Give the drinking-water without any antibacterials.Be about the 10% of its weight according to the daily amount of drinking water of sick pig, calculate trial drug it is low, in, The dose of required investment in high dose group (I, II, III group) and control drug group (IV group) sick pig 1L drinking water.Each group sick pig Medical fluid is freely drunk, is used in conjunction 5.Medical fluid is replaced once daily, during entire treatment, no longer provides other any drinks to sick pig Use water source.All test sick pigs feed the feed without any antibacterials.Colony house cleans once daily, uses every 3 days Hundred poisoning spraying disinfections are primary.Other feeding managements are routinely carried out by pig farm.

3, evaluation index

(1) before observing and recording medication, medication the 5th day, the clinical symptoms for deactivating medicine sick pig on the 5th: such as the state of mind, food Desire, respiratory symptom (cough, stream nose liquid and expiratory dyspnea), excreta, body temperature etc..The clinical symptoms of each group sick pig are commented Point (0- normal condition, 1- is slight, 2- moderate, and 3- is serious), the average of sick pig in calculating group, in comparative group each time point and The significance of difference between group between each time point symptom score.

(2) lesion observation and pathogenicbacteria separation: being discontinued the 5th, and each group sick pig randomly chooses 5 and butchers, and observation thoracic cavity is dirty Device lesion scores by following standard, the average of sick pig in calculating group, compares thoracic organ lesion score between each group The significance of difference.The lung and pleural effusion for acquiring each head pig simultaneously carry out detection of pathogens.Thoracic organ lesion score standard: 1. Each leaf of lungs and pleura color are normal, and no obvious eye sees lesion (0 point)；2. each leaf of lungs and pleura color are normal, only Disperse, the aubergine area (1 point) of small area；3. lungs and pleura have congested, oedema to be even dispersed in bleeding, a small amount of hydrops (2 in thoracic cavity Point)；4. lungs and pleura have large area lesion, consolidation occurs for lung, or even sticks together；Thoracic cavity volume hydrops and fibrin seep Object (3 points) out.

4, curative effect determinate standard

(1) cure: after continuous use 5 days, sick pig spirit, appetite restore normal, and body temperature, breathing also restore normal (symptom Scoring=0), weight obviously increases；Dissect is without specific lesions (scoring≤1)；Pathological material of disease is detected without pathogen.

Cure rate=(pig's head number/group innerlich anwenden pig's head number is cured in group) × 100%

(2) effectively: after continuous use 5 days, sick pig spirit, appetite are returned to normal, body temperature ,≤1 point of breathing scoring；Body It increased again；Dissect lesion score < 2 point；Pathological material of disease is detected without pathogen.

Efficient=(effectively pig's head number/group innerlich anwenden pig's head number in group) × 100%

(3) invalid: after continuous use 5 days, sick pig spirit, appetite are restored without obvious, and body temperature, respiratory symptom do not improve very To more deterioration or dead, scoring >=2；Dissect lesion score >=2 point；The detection of pathological material of disease pathogen.

5, interpretation of result

(1) clinical symptoms

The clinical symptoms of each group sick pig are observed and recorded during test daily, before calculating medication, medication the 5th day, are discontinued the 5th The symptom score mean value of day each group sick pig, it is for statistical analysis, it the results are shown in Table 1.

1 data of table show that the symptom score of each group sick pig is without significant difference (P > 0.05) before medication.Pass through drinking water administration 5 In the future, the symptom score of no medicine control group (V group) is extremely significant is higher than Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E Compound combines low, middle and high dose groups (I, II, III group) and Doxycycline Hyclate group (IV group) (P < 0.01)；The how western ring of hydrochloric acid The symptom score that element, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combine middle and high dosage group (II, III group) is substantially less than Doxycycline Hyclate group (IV group) (0.01 < P < 0.05), without significant difference between low dose group (I group) and Doxycycline Hyclate group (P > 0.05).Medicine is deactivated after 5 days, the symptom score of no medicine control group is still extremely significant to be higher than Doxycycline Hyclate, honeysuckle extraction Object, Baical Skullcap root P.E compound medicine combination low, middle and high dose groups and Doxycycline Hyclate group (P < 0.01)；Doxycycline Hyclate The symptom score of group is significantly higher than Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine and combines middle and high dosage Group (0.01 < P < 0.05).

After continuous use 5 days and drug withdrawal the 5th day, the symptom score of each group sick pig has reduction.Wherein Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combination low, middle and high dose groups (I, II, III group) and Doxycycline Hyclate group The symptom score of (IV group) declines extremely significant (P < 0.01)；Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine The symptom score that object combines low dose group declines significant (0.01 < P < 0.05).Symptom without medicine control group sick pig during test Scoring also has decline, but obvious not as good as each medication group.

The above results show to give Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E by drinking-water in continuous 5 days Compound medicine combination and Doxycycline Hyclate, can significantly improve Actinobacillus pleuropneumoniae sick pig the poor, reduction of ingesting of spirit, The clinical symptoms such as body temperature raising, expiratory dyspnea.Wherein low dosage Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E are multiple The effect of square pharmaceutical composition is suitable with Doxycycline Hyclate, and middle and high dosage Doxycycline Hyclate, Honegsukle flower P.E, radix scutellariae mention The effect no significant difference for taking object compound medicine to combine, is superior to Doxycycline Hyclate.

(2) lesion observation and pathogenicbacteria separation

It is discontinued the 5th, each group sick pig randomly chooses 5 and butchers, and observes thoracic organ lesion and presses scale, calculating group Interior scoring mean value compares the significance of difference of each group scoring；The lung and pleural effusion for acquiring each head pig simultaneously carry out cause of disease bacterial examination It surveys, the results are shown in Table 2.

The drug withdrawal part sick pig thoracic cavity lesion score on the 5th of table 2 and pathogen detection situation (n=5)

2 data of table as it can be seen that Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combination it is basic, normal, high The thoracic cavity lesion score of dosage group (I, II, III group) and Doxycycline Hyclate (IV group) disease≤1 point, and have 3 without medicine control group Thoracic cavity lesion score >=2 point of head sick pig；It is 0 point that middle and high dosage group has the thoracic cavity lesion score of 4 pigs respectively, low dose group The thoracic cavity lesion score for having 3 pigs is 0 point.Each group sick pig thoracic cavity lesion score mean value compares, the thoracic cavity of no medicine control group sick pig Extremely significant Doxycycline Hyclate, Honegsukle flower P.E, the Baical Skullcap root P.E compound medicine of being higher than of lesion score combines basic, normal, high dose Amount group (I, II, III group) (P < 0.01) is significantly higher than Doxycycline Hyclate group (IV group) (0.01 < P < 0.05)；The how western ring of hydrochloric acid The thoracic cavity lesion that element, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combine low, middle and high dose groups (I, II, III group) is commented Divide and be below Doxycycline Hyclate group, but difference is not significant (P > 0.05).Each group butchers the lung of sick pig and pleural effusion is trained through TSA Support base detection, each medication group (including the combination of Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine and hydrochloric acid Doxycycline) for sick pig without actinobacillus pleuropneumoniae and the detection of other pathogens, no medicine control group has 2 sick pigs detection chests Film Actinobacillus.

The above results show that continuous 5 daily drink of sick pig gives Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E Compound medicine combination and Doxycycline Hyclate, not only can effectively remove its intracorporal actinobacillus pleuropneumoniae；It may additionally facilitate The improvement of sick pig thoracic cavity lesion is even fully recovered.Wherein Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine group The above-mentioned effect closed is better than Doxycycline Hyclate, especially with middle and high dosage Doxycycline Hyclate, Honegsukle flower P.E, radix scutellariae The effect of compound extract pharmaceutical composition is preferred.

(3) efficient and cure rate

The clinical symptoms of each group sick pig improve after comprehensive drug withdrawal 5 days and recovery situation, thoracic cavity lesion and pathogen detect feelings Condition carries out efficacy determination by given standard, can get the effective percentage and cure rate of each group sick pig, the results are shown in Table 3.

Table 3 be discontinued after after 5 days each group sick pig effective percentage and more rate (n=20)

3 data of table show that Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combine middle and high dosage Group (II, III group) effective percentage it is extremely significant be higher than not medication control group (P < 0.01), Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combines low dose group (I group), the effective percentage of Doxycycline Hyclate group (IV group) is significantly higher than and does not have to Medicine control group (V group) (0.01 < P < 0.05)；Effective percentage between other each groups is without significant difference (P > 0.05).The how western ring of hydrochloric acid It is how western that the cure rate that element, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combine high dose group (III group) is significantly higher than hydrochloric acid Ring element group (IV group) (0.01 < P < 0.05), it is extremely significant to be higher than not medication control group (V group) (P < 0.01)；Doxycycline Hyclate, gold Honeysuckle flower extract, the cure rate of Baical Skullcap root P.E compound medicine combination middle dose group (II group) are extremely significant better than not medication control group (V group) (P < 0.01)；Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combination low dose group (I group), The cure rate of Doxycycline Hyclate group is significantly higher than not medication control group (V group) (0.01 < P < 0.05)；Healing between other each groups Rate is without significant difference (P > 0.05).

In summary test result, the drug Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine Soluble powder has good therapeutic effect to the contagious pleuropneumonia of swinery natural infection.How western the hydrochloric acid of basic, normal, high dosage is Ring element, Honegsukle flower P.E, the combination of Baical Skullcap root P.E compound medicine can effectively remove the intracorporal pig pleuropneumonia unwrapping wire of sick pig Bacillus promotes the improvement of sick pig thoracic cavity lesion even to fully recover, significantly improves sick pig clinical symptoms.And how western middle and high dosage hydrochloric acid is Ring element, Honegsukle flower P.E, the combination of Baical Skullcap root P.E compound medicine effective percentage be 100%, cure rate is up to 95% or more；Low dose Amount Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine combine and the effective percentage of Doxycycline Hyclate group reaches 90% or more, cure rate is up to 70% or more.Middle and high dosage Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E compound medicine Combined therapeutic effect is superior to Doxycycline Hyclate.

Claims (3)

1. a kind of for treating the antibiotic preparation of porcine contagious pleuropneumonia, which is characterized in that in the preparation of 100 mass fractions In, each component is according to the mass fraction are as follows:

Doxycycline Hyclate 2~20,

Honegsukle flower P.E 4~40,

Baical Skullcap root P.E 2.5~25

Glucose surplus.

2. according to claim 1 for treating the antibiotic preparation of porcine contagious pleuropneumonia, which is characterized in that 100 In the preparation of mass fraction, each component is according to the mass fraction are as follows:

Doxycycline Hyclate 10,

Honegsukle flower P.E 20,

Baical Skullcap root P.E 12.5,

Glucose surplus.

3. a kind of prepare the method as claimed in claim 1 or 2 for treating the antibiotic preparation of porcine contagious pleuropneumonia, It is characterized in that, preparation carries out as follows:

A, Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and glucose are weighed by formula；

B, the above component be crushed into 24 meshes respectively；

C, Doxycycline Hyclate, Honegsukle flower P.E, Baical Skullcap root P.E and the appropriate glucose after sieving is pre- in mixing machine 15 minutes mixed, the glucose for adding surplus mixes 30 minutes, up to product after mixing.