Summary of the invention
The object of the present invention is to provide a kind of stable spectinomycin hydrochloride for animals, the preparation method of lincomycin hydrochloride injection.The present invention carries out enclose with spectinomycin hydrochloride with cyclodextrin, can significantly improve the stability of spectinomycin hydrochloride in aqueous solution, thereby has guaranteed stability and the curative effect of spectinomycin hydrochloride, lincomycin hydrochloride injection.The present invention has broken through the key technology difficult problem of spectinomycin hydrochloride, lincomycin hydrochloride compound injection, preparation method of the present invention has guaranteed quality and the drug effect that this series products is good, be the infection such as veterinary clinic treatment poultry antibacterial, mycoplasma, the medicine of steady quality, determined curative effect is provided.
The objective of the invention is to be achieved through the following technical solutions:
The invention provides the preparation method of a kind of spectinomycin hydrochloride for animals, lincomycin hydrochloride injection, it is characterized in that spectinomycin hydrochloride is carried out enclose with cyclodextrin, the spectinomycin hydrochloride clathrate of making is prepared into compound injection with lincomycin hydrochloride again.
Wherein, the weight proportion of spectinomycin hydrochloride and cyclodextrin be preferably 30: 1~1: 20.
Further, the weight proportion of spectinomycin hydrochloride and cyclodextrin be preferably 15: 1~1: 10.
Used lincomycin hydrochloride and the weight proportion of spectinomycin hydrochloride among the present invention, the weight proportion adding gets final product routinely, but be the synergistic function of better bringing into play the two, reaching preferably clinical effectiveness, the weight proportion of spectinomycin hydrochloride and lincomycin hydrochloride can be 20: 1~and 1: 10.
Further, the weight proportion preferable range of spectinomycin hydrochloride and lincomycin hydrochloride is 10: 1~1: 5.
Further, the weight proportion of spectinomycin hydrochloride and lincomycin hydrochloride is 2: 1.
The used cyclodextrin of the present invention can be in alpha-cyclodextrin, hydroxyethyl-β-cyclodextrin, HP-β-CD, DM-β-CD, TM-β-CD, the gamma-cyclodextrin any one.
The preparation method of spectinomycin hydrochloride for animals of the present invention, lincomycin hydrochloride injection, its preparation process is as follows:
(1) get an amount of water for injection, add by weight ratio cyclodextrin dissolving, add spectinomycin hydrochloride, 40-60 ℃ rapid stirring 20-30 minute;
(2) add lincomycin hydrochloride, stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming or Co 60 ray sterilizing.
The preparation method of spectinomycin hydrochloride for animals of the present invention, lincomycin hydrochloride injection, its preparation also can be carried out as follows:
(1) cyclodextrin is made 50 ℃ saturated aqueous solution, added by weight ratio spectinomycin hydrochloride, stirred at least 30 minutes, be cooled to rapidly below 4 ℃, filter, drying namely gets the clathrate of spectinomycin hydrochloride;
(2) get an amount of water for injection, add the spectinomycin hydrochloride clathrate, stirring and dissolving adds the lincomycin hydrochloride stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming or Co 60 ray sterilizing.
The present invention is different from the preparation method of traditional compound injection, but with the processing of spectinomycin hydrochloride by cyclodextrin inclusion compound, obtains stable clathrate, again itself and lincomycin hydrochloride is prepared into compound injection.Preparation method of the present invention is passed through to improve the stability of spectinomycin hydrochloride in aqueous solution, thereby has guaranteed the Quality and curative effect of product.Preparation method step of the present invention is simple, but broken through the key technology difficult problem of spectinomycin hydrochloride, lincomycin hydrochloride compound injection, thereby quality and drug effect that this series products is good have been guaranteed, be the infection such as veterinary clinic treatment poultry antibacterial, mycoplasma, the medicine of steady quality, determined curative effect is provided.
, it should be understood that described embodiment only is for the present invention is described, rather than limit the scope of the invention by any way more specific description the present invention by the following example.
The specific embodiment
Embodiment 1
Prescription:
Spectinomycin hydrochloride 10g
Lincomycin hydrochloride 5g
HP-β-CD 5g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) gets water for injection 70mL, add by weight ratio HP-β-CD, add spectinomycin hydrochloride, 50 ℃ of rapid stirrings 30 minutes;
(2) add lincomycin hydrochloride, stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming.
Embodiment 2
Prescription:
Spectinomycin hydrochloride 4g
Lincomycin hydrochloride 2g
Hydroxyethyl-β-cyclodextrin 40g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) the hydroxyethyl-β-cyclodextrin cyclodextrin is prepared into 50 ℃ of saturated solutions, adds by weight ratio spectinomycin hydrochloride, stirred 30 minutes, be cooled to rapidly below 4 ℃, filter, drying gets the spectinomycin hydrochloride clathrate;
(2) get water for injection 70mL, add the spectinomycin hydrochloride clathrate, stirring and dissolving adds the lincomycin hydrochloride stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter, 60 ray sterilizings are bored in embedding.
Embodiment 3
Prescription:
Spectinomycin hydrochloride 30g
Lincomycin hydrochloride 15g
Gamma-cyclodextrin 1g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) gets water for injection 70mL, add by weight ratio gamma-cyclodextrin, add spectinomycin hydrochloride, 60 ℃ of rapid stirrings 30 minutes;
(2) add lincomycin hydrochloride, stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming.
Embodiment 4
Prescription:
Spectinomycin hydrochloride 2g
Lincomycin hydrochloride 1g
Alpha-cyclodextrin 40g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) the alpha-cyclodextrin cyclodextrin is prepared into 50 ℃ of saturated solutions, adds by weight ratio spectinomycin hydrochloride, stirred 30 minutes, be cooled to rapidly below 4 ℃, filter, drying gets the spectinomycin hydrochloride clathrate;
(2) get water for injection 70mL, add the spectinomycin hydrochloride clathrate, stirring and dissolving adds the lincomycin hydrochloride stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming.
Embodiment 5
Prescription:
Spectinomycin hydrochloride 15g
Lincomycin hydrochloride 7.5g
DM-β-CD 1g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) gets water for injection 70mL, add by weight ratio DM-β-CD, add spectinomycin hydrochloride, 40 ℃ of rapid stirrings 30 minutes;
(2) add lincomycin hydrochloride, stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, Co 60 ray sterilizing.
Embodiment 6
Prescription:
Spectinomycin hydrochloride 10g
Lincomycin hydrochloride 5g
TM-β-CD 4g
Antioxidant is an amount of
Water for injection adds to 100mL
Preparation method:
(1) gets water for injection 70mL, add by weight ratio TM-β-CD, add spectinomycin hydrochloride, 50 ℃ of rapid stirrings 30 minutes;
(2) add lincomycin hydrochloride, stirring and dissolving;
(3) water for injection that takes a morsel adds antioxidant, stirring and dissolving;
(4) merge (2), (3) liquid, use the water for injection standardize solution;
(5) filter embedding, filtering with microporous membrane degerming.
Experimental example 1 is according to the spectinomycin hydrochloride of embodiment 1 preparation, the accelerated test study on the stability of lincomycin hydrochloride injection
The preparation of control drug: get water for injection 70mL, add spectinomycin hydrochloride 10g, stirring and dissolving; Add lincomycin hydrochloride 4g, stirring and dissolving; Add with the water-soluble antioxidant of a small amount of injection; Use the water for injection standardize solution; Filter embedding, filtering with microporous membrane degerming.
Test method: the method according to embodiment 1 prepares spectinomycin hydrochloride, lincomycin hydrochloride injection, with the stability of control drug comparison under the accelerated test condition.40 ± 2 ℃ of temperature, placed six months under the condition of relative humidity 75 ± 5%.Sampling in the 1st, 2,3,6 month once, detect by stable high spot reviews project respectively.
Result of the test: the comparative result for preparing the stability of spectinomycin hydrochloride, lincomycin hydrochloride injection and control drug according to the method for embodiment 1 sees Table 1
Table 1 accelerated test result
Experimental example 2 is investigated according to the spectinomycin hydrochloride of embodiment 1 preparation, the long-time stability of lincomycin hydrochloride injection
The preparation of control drug: get water for injection 70mL, add spectinomycin hydrochloride 10g, stirring and dissolving; Add lincomycin hydrochloride 4g, stirring and dissolving; Add with the water-soluble antioxidant of a small amount of injection; Use the water for injection standardize solution; Filter embedding, filtering with microporous membrane degerming.
Test method: the method according to embodiment 1 prepares spectinomycin hydrochloride, lincomycin hydrochloride injection, with the stability of control drug comparison under the long term test condition.25 ± 2 ℃ of temperature, placed 12 months under the condition of relative humidity 60 ± 5%.Sampling in the 3rd, 6,9,12 month once, detect by stable high spot reviews project respectively.
Result of the test: the comparative result for preparing the stability of spectinomycin hydrochloride, lincomycin hydrochloride injection and control drug according to the method for embodiment 1 sees Table 2
Table 2 long-term test results
Experimental example 3 is according to the spectinomycin hydrochloride of embodiment 1 preparation, the Effect tests of lincomycin hydrochloride injection clinical treatment respiratory tract infection
The preparation of control drug: get water for injection 70mL, add spectinomycin hydrochloride 10g, stirring and dissolving; Add lincomycin hydrochloride 4g, stirring and dissolving; Add with the water-soluble antioxidant of a small amount of injection; Be settled to 100mL with water for injection; Filter embedding, filtering with microporous membrane degerming.
Test method: choose body weight 25 ± 5kg, be diagnosed as 90 of the growing and fattening pigs of respiratory tract infection, be divided at random 3 groups, be i.e. I, II, III group, 30 every group.The intramuscular injection of I group is according to spectinomycin hydrochloride, the lincomycin hydrochloride injection of embodiment 1 preparation, and per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days; II group intramuscular injection control drug, per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days.The III group is blank group, not administration.
Result of the test: the clinical test results for preparing spectinomycin hydrochloride, lincomycin hydrochloride injection and control drug according to the method for embodiment 1 sees Table 3
The clinical test results of table 3 treatment respiratory tract infection
Group |
Experiment number (head) |
Cure number (head) |
Cure rate (%) |
Good revolution (head) |
Improvement rate (%) |
Invalid number |
Inefficiency |
I |
30 |
30 |
100 |
0 |
0 |
0 |
0 |
II |
30 |
20 |
66.7 |
7 |
23.3 |
3 |
10 |
III |
30 |
0 |
0 |
3 |
10 |
27 |
90 |
The symptoms of respiratory disease such as the cough of I group pig, rapid breathing obviously alleviate in the process of the test, and the mental status is clearly better, and does not find any adverse effect.II group porcine respiratory disease sx↓, the mental status takes a turn for the better, and does not find obvious adverse effect.III group porcine respiratory disease symptom does not alleviate, and spirit is depressed.
Experimental example 4 is according to the spectinomycin hydrochloride of embodiment 1 preparation, the Effect tests of lincomycin hydrochloride injection clinical treatment piglet diarrhea
The preparation of control drug: get water for injection 70mL, add spectinomycin hydrochloride 10g, stirring and dissolving; Add lincomycin hydrochloride 4g, stirring and dissolving; Add with the water-soluble antioxidant of a small amount of injection; Be settled to 100mL with water for injection; Filter embedding, filtering with microporous membrane degerming.
Test method: choose body weight 14 ± 2kg, 90 of the ablactational baby pig of symptom of diarrhea are arranged, be divided at random 3 groups, be i.e. I, II, III group, 30 every group.The intramuscular injection of I group is according to spectinomycin hydrochloride, the lincomycin hydrochloride injection of embodiment 1 preparation, and per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days; II group intramuscular injection control drug, per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days; The III group is blank group, not administration.
Result of the test: the clinical test results for preparing spectinomycin hydrochloride, lincomycin hydrochloride injection and control drug according to the method for embodiment 1 sees Table 4
The clinical test results of table 4 treatment piglet diarrhea
I group piglet feed intake obviously increases in the process of the test, the mental status is clearly better, and does not find any adverse effect.II group piglet feed intake increases, the mental status slightly take a favorable turn, and does not find obvious adverse effect.III organizes piglet appetite, the mental status is relatively poor.
Experimental example 5 is according to the spectinomycin hydrochloride of embodiment 1 preparation, the Effect tests of lincomycin hydrochloride injection clinical treatment sow triad in puerperal
The preparation of control drug: get water for injection 70mL, add spectinomycin hydrochloride 10g, stirring and dissolving; Add lincomycin hydrochloride 4g, stirring and dissolving; Add with the water-soluble antioxidant of a small amount of injection; Be settled to 100mL with water for injection; Filter embedding, filtering with microporous membrane degerming.
Test method: choose body weight 200 ± 10kg, be diagnosed as 45 of the sows of triad in puerperal, be divided at random 3 groups, be i.e. I, II, III group, 15 every group.The intramuscular injection of I group is according to spectinomycin hydrochloride, the lincomycin hydrochloride injection of embodiment 1 preparation, and per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days; II group intramuscular injection control drug, per kilogram of body weight injection 0.1mL once a day, is used in conjunction three days; The III group is blank group, not administration.
Result of the test: the clinical test results according to spectinomycin hydrochloride, lincomycin hydrochloride injection and the control drug of the preparation of the method for embodiment 1 sees Table 5
The clinical test results of table 5 treatment sow triad in puerperal
Group |
A test sow number |
Cure number (head) |
Cure rate (%) |
Good revolution |
Improvement rate |
Invalid number |
Inefficiency |
I |
15 |
15 |
100 |
0 |
0 |
0 |
0 |
II |
15 |
11 |
73.3% |
3 |
20 |
1 |
6.7 |
III |
15 |
0 |
0 |
2 |
13.3 |
13 |
86.7 |
I group sow appetite, the mental status are clearly better in the process of the test, do not find any adverse effect.II group sow appetite, the mental status slightly take a favorable turn, and do not find obvious adverse effect.III organizes sow appetite, the mental status is relatively poor.