CN101219209A - Insulin-protamine zinc injection and method for preparing the same - Google Patents
Insulin-protamine zinc injection and method for preparing the same Download PDFInfo
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- CN101219209A CN101219209A CNA2007101734303A CN200710173430A CN101219209A CN 101219209 A CN101219209 A CN 101219209A CN A2007101734303 A CNA2007101734303 A CN A2007101734303A CN 200710173430 A CN200710173430 A CN 200710173430A CN 101219209 A CN101219209 A CN 101219209A
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Abstract
The invention pertains to a pharmaceutical preparation field, and in particular relates to a zinc protamine insulin ampoule injection and a preparation method thereof. The zinc protamine insulin ampoule injection comprises insulin, isotonizing agent, antiseptic agent, pH regulator, protamine sulfate and bi-distilled water for injection, wherein, the bi-distilled water for injection contains divalent zinc salt and the concentration of zinc ion is 0.01-0.04g per100000IU of insulin. The injection of the invention has the advantages that minim zinc ion is added into the insulin to form a stable polymer, which stabilizes the insulin and has a prolonged curative effect; the invention has simple, scientific and reasonable preparation and easy manipulation. The insulin can exist in two patterns: firstly, in liquor with quick effect; secondly, combining with protamine sulfate and in precipitation with action characters of both two insulin preparations, which reduces injection time and pain caused by rejection. Animal insulin is used for the injection, thus reducing the cost.
Description
Technical field
The invention belongs to field of medicine preparations, relate in particular to a kind of protamine zinc insulin injection and preparation method thereof.
Background technology
Diabetes are the 4th fatal diseases in the whole world, are the 3rd lethal factors in China.The whole world has 1.94 hundred million people to suffer from diabetes approximately at present.China has 2,500 ten thousand diabeticss approximately, if add potential crowd, the sum that threatened by diabetes reaches 4,000 ten thousand people.Expect 2025, diabetes will become one of disease that number of patients is maximum in the world, and world wide will have 3.3 hundred million people to suffer from diabetes when the time comes, and Chinese diabetics will reach 5,000 ten thousand people.
Since nineteen twenties is adopted insulin, constantly obtained the progress of advancing by leaps and bounds for treatment of diabetes.
The insulin classification:
Medicinal insulin mainly is divided into according to the source: 1) animal insulin, as bovine insulin (bovine insulin extracts from Pancreas Bovis seu Bubali), Iletin II (Lilly) (Iletin II (Lilly) is to extract from Pancreas Sus domestica); 2) insulin human is as half biosynthetic human insulin, gene recombinaton insulin human; 3) insulin analog.
According to difference action time, insulin can be divided into: 1) fugitive (quick-acting) insulin: effect peak after injection 1～3 hour, and acting duration is 5～7 hours, as neutral insulin; 2) intermediate-acting insulins: effect peak after injection 6～10 hours, acting duration is 18～24 hours, as isophane insulin; 3) protamine zine insulin: effect peak after injection 10～15 hours, acting duration is 28～36 hours; 4) premix insulin: short-acting insulin preparation and intermediate-acting insulins preparation are carried out the mixing of different proportion, produce onset time and the effect marginal premix insulin preparation of holding time.Therefore need not patient before the injection mixes voluntarily again.
Applicant of the present invention discloses a kind of preparation of double timephase neo-insulin zinc injection liquid in its number of patent application 200610116408.0, wherein, neutral insulin liquid mixes with 3: 7 with isophane insulin solution.Insulin exists with two kinds of forms in this patent application, and is a kind of in solution, bringing into play quick-acting effects; A kind of combination with protamine sulfate exists in the precipitation, have the time phase characteristics of intermediate-acting insulins, possessing like this has the effect of two kinds of insulin preparations characteristics, greatly facilitates the diabetes patient, reduced frequency injection and the misery of bringing thus and inconvenient, but stability is not enough.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of protamine zinc insulin injection, and the mixing for quick-acting and middle effect two specific character preparations comprises zinc salt in the water for injection.
Another technical problem to be solved by this invention is to provide a kind of preparation method of this insulin zinc protamine.
The present invention solves the problems of the technologies described above the technical scheme that is adopted: a kind of protamine zinc insulin injection, component comprises insulin, isotonic agent, antiseptic, pH regulator agent, protamine sulfate, wherein, comprise divalent zinc salt in the described water for injection, the concentration of described zinc ion is 0.01～0.04g/100000IU, wherein, the concentration of the described zinc ion of insulin is preferably 0.01～0.025g/100000IU insulin.Adding the trace zinc ion can form stable polymer with insulin, increases the stability of insulin, and has the effect that prolongs curative effect.
On the basis of such scheme, described zinc salt is the solubility divalent zinc salt, comprises a kind of or its combination in zinc acetate, zinc bromide, zinc chloride, zinc iodide, zinc fluoride, the zinc sulfide etc.
Described protamine zinc insulin injection comprises following component among the insulin 100000IU:
Isotonic agent 35～45g
Antiseptic 5.5～7g
PH regulator agent 12～12.5g
Protamine sulfate 0.15～0.6g
Surplus is the water for injection that comprises divalent zinc ion, and pH value is 6.9～7.8.
Isotonic agent with measuring can for: 35,36,37,38,39,40,41,42,43,44, the 45g/100000IU insulin.
The consumption of antiseptic is specifically as follows: 5.5,5.6,5.7,5.8,5.9,6.0,6.1,6.2,6.3,6.4,6.5,6.6,6.7,6.8,6.9, and the 7.0g/100000IU insulin.
The consumption of pH regulator agent is specifically as follows: 12,12.05,12.1,12.15,12.2,12.25,12.3,12.35,12.4,12.45, and the 12.5g/100000IU insulin.
The consumption of protamine sulfate is specifically as follows: 0.15,0.18,0.2,0.22,0.25,0.27,0.3,0.33,0.35,0.38,0.4,0.42,0.45,0.48,0.5,0.53,0.55,0.57, and 0.6g.Preferable amount is 0.2～0.45g/100000IU insulin.
Described insulin is Iletin II (Lilly) or bovine insulin; Described isotonic agent is a glycerol; Described antiseptic is phenol and metacresol; Described pH regulator agent is sodium hydrogen phosphate or its crystalline solid.
PH regulator agent of the present invention has excellent pH dash adjustment effect, mainly is the multiple ionization characteristic of having utilized sodium hydrogen phosphate.The pH regulator agent can also be sodium hydroxide or hydrochloric acid.
On the basis of such scheme, described insulin is an isophane insulin.
Preparation method at above-mentioned protaphane beef ampoule, comprising the steps: A, the smart powder of isophane insulin is added pH value is in 1.8～2.2 an amount of water for injection, add the zinc salt stirring and dissolving, add the aqueous solution for injection that contains isotonic agent, antiseptic, protamine sulfate, mix adjust pH to 2.5～3.0.
B, pH regulator agent are dissolved with water for injection, are made into volumetric soiutions by above-mentioned prescription, with hydrochloric acid adjust pH to 7.8～8.2.
With A and the mixed isophane insulin solution of making of B.
Wherein, comprise among steps A, the B that solution that steps A, B are made is respectively through 0.2～0.25 μ m membrane filtration degerming.
On the basis of such scheme, described insulin comprises the mixture of neutral insulin and isophane insulin, and wherein, the proportioning of neutral insulin and isophane insulin is 30: 70 or 50: 50.
Preparation method at above-mentioned mixing regular iletin comprises the steps:
(1) preparation neutral insulin liquid:
It is in 1.8～2.2 the water for injection that the smart powder of neutral insulin is joined pH value, add the zinc salt stirring and dissolving, add the aqueous solution for injection that contains isotonic agent, antiseptic and pH regulator agent, add the injection water and be made into volumetric soiutions, with hydrochloric acid adjust pH to 6.5～7.5, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of isophane insulin is joined pH value is in 1.8～2.2 the water for injection, adds the zinc salt stirring and dissolving, adds the aqueous solution for injection that contains isotonic agent, antiseptic, protamine sulfate, mixes adjust pH to 2.5～3.0;
B, with the agent of water for injection dissolving pH regulator, add the injection water and be made into volumetric soiutions, with hydrochloric acid adjust pH to 7.8～8.2;
A and B are mixed, make protaphane beef ampoule;
(3) neutral insulin liquid and isophane insulin solution is even with 3: 7 or 5: 5 mixed, make protamine zinc insulin injection.
Wherein, in the described neutral insulin liquid preparation, neutral insulin liquid is through 0.2～0.25 μ m membrane filtration degerming.
At the purposes of above-mentioned protamine zinc insulin injection, as the injection of treatment diabetes.
The invention has the beneficial effects as follows:
1, the present invention not only has the characteristics of phase when two, that is: insulin exists with two kinds of forms, and is a kind of in solution, bringing into play quick-acting effects; A kind of combination with protamine sulfate exists in the precipitation, has the time phase characteristics of intermediate-acting insulins, and possessing like this has the effect of two kinds of insulin preparations characteristics, greatly facilitates the diabetes patient, reduced frequency injection and bring thus painful and inconvenient; Also can form stable polymer with insulin, increase the stability of insulin, and have the effect that prolongs curative effect because add the trace zinc ion;
2, insulin adopts animal insulin, counterpart's insulin low price, the financial burden that can alleviate diabetics in this product;
3, the preparation of this product is simple, scientific and reasonable, easily operation.
The specific embodiment
One, protaphane beef ampoule preparation:
Embodiment 1
Table 1
| Prescription | Metering |
| Isophane insulin | 100000IU |
| Glycerol | 35g |
| Phenol and metacresol | 5.5g |
| Zinc chloride | 20.9mg |
| Sodium hydrogen phosphate | 12g |
| Protamine sulfate | 0.3g |
| Water for injection | 2500ml |
Preparation method comprises the steps:
A, by prescription the smart powder of isophane insulin to be joined pH value be in 2.0 an amount of water for injection, add the zinc chloride stirring and dissolving again, the aqueous solution that contains glycerol, antiseptic, protamine sulfate that adding prepares by table 1, be made into 1250ml solution, mix, make the zinc total concentration remain on the 0.01g/100000IU insulin, adjust pH to 2.5 is through 0.22 μ m membrane filtration degerming.
B, sodium hydrogen phosphate are made into 1250ml solution by scale 1 amount, with 1mol/L hydrochloric acid adjust pH to 8.0, through 0.22 μ m membrane filtration degerming.
A and B is mixed, start stirring and make it mix homogeneously, make isophane insulin solution, it is qualified surveying pH value to 6.9.
Embodiment 2
Table 2
| Prescription | Metering |
| Isophane insulin | 100000IU |
| Glycerol | 35g |
| Phenol and metacresol | 5.5g |
| Zinc chloride | 62.7mg |
| Sodium hydrogen phosphate | 12g |
| Protamine sulfate | 0.6g |
| Water for injection | 2500ml |
Preparation method comprises the steps:
A, by table 2 prescription the smart powder of isophane insulin to be joined pH value be in 2.0 an amount of water for injection, add the zinc chloride stirring and dissolving again, the aqueous solution for injection that contains glycerol, antiseptic, protamine sulfate that adding prepares in advance by table 2, be made into 1250ml solution, mix, make the zinc total concentration remain on the 0.03g/100000IU insulin, adjust pH to 3.0 is through 0.22 μ m membrane filtration degerming.
B, sodium hydrogen phosphate are dissolved in the water for injection according to quantity, are made into 1250ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0, through 0.22 μ m membrane filtration degerming.
A and B is mixed, start to stir and make it mix homogeneously, make isophane insulin solution, survey pH value and be 7.5 for qualified.
Embodiment 3
Table 3
| Prescription | Metering |
| Insulin | 100000u |
| Glycerol | 35g |
| Phenol and metacresol | 5.5g |
| Zinc chloride | 83.6mg |
| Sodium hydrogen phosphate | 12g |
| Protamine sulfate | 0.45g |
| Water adds to | 2500ml |
Preparation method comprises the steps:
A, by table 3 the smart powder of isophane insulin to be joined pH value be in 2.0 an amount of water for injection, add the zinc chloride stirring and dissolving again, the aqueous solution that contains glycerol, antiseptic, protamine sulfate that adding prepares in advance by table 3, be made into 1250ml solution, mix, make the zinc total concentration remain on the 0.04g/100000IU insulin, adjust pH to 2.7 is through 0.22 μ m membrane filtration degerming.
The sodium hydrogen phosphate of B, the dissolved formula ratio of usefulness water for injection is made into 1250ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0, through 0.22 μ m membrane filtration degerming.
A and B is mixed, start to stir and make it mix homogeneously, make isophane insulin solution, survey pH value and be 7.2 for qualified.
Two, neutral insulin liquid: isophane insulin solution mixing ratio is 3: 7 injection preparation:
Embodiment 4
Table 4
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 30000IU | ?100000u | |
| Isophane insulin | 70000IU | ||
| Glycerol | 10.5g | 24.5g | ?35g |
| Phenol and metacresol | 1.65g | 3.85g | ?5.5g |
| Zinc chloride | 6.3mg | 14.6mg | ?20.9mg |
| Sodium hydrogen phosphate | 3.6g | 8.4g | ?12g |
| Protamine sulfate | 0.21g | ?0.21g | |
| Water for injection | 750ml | 1750ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 30000IU neutral insulin is joined pH value, add 6.3mg zinc chloride stirring and dissolving again, the aqueous solution that contains 10.5g glycerol, 1.65g phenol and metacresol, 3.6g sodium hydrogen phosphate that adding prepares in advance by table 4, add the injection water and be made into 750ml solution, with hydrochloric acid adjust pH to 6.9, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution α
A, the smart powder of 70000IU isophane insulin is joined pH value is in 2.0 the water for injection, add 14.6mg zinc chloride stirring and dissolving, add and prepare the aqueous solution for injection that contains 24.5g glycerol, 3.85g phenol and metacresol and 0.21g protamine sulfate in advance, be made into 875ml solution, mix adjust pH to 2.5;
B, with water for injection dissolving 8.4g sodium hydrogen phosphate, be made into 875ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
Surveying pH value to 6.9 be certified products, and can suitably to adjust neutral insulin solution pH value extremely qualified as defective.Insulin content in the analytical solution can suitably be adjusted A, the B ratio is qualified until insulin content.According to qualified ratio under stirring state is that slowly to add A liquid be to mix in the neutral insulin solution to import bottling department after 3 hours to isophane insulin solution with B liquid.
Embodiment 5
Table 5
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 30000IU | ?100000IU | |
| Isophane insulin | ?70000IU | ||
| Glycerol | 13.5g | ?31.5g | ?45g |
| Phenol and metacresol | 2.1g | ?4.9g | ?7g |
| Zinc chloride | 18.9mg | ?43.8mg | ?62.7mg |
| Sodium hydrogen phosphate | 3.75g | ?8.75g | ?12.5g |
| Protamine sulfate | ?0.42g | ?0.42g | |
| Water for injection | 750ml | ?1750ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 30000IU neutral insulin is joined pH value, add 18.9mg zinc chloride stirring and dissolving again, the aqueous solution for injection that contains 13.5g glycerol, 2.1g phenol and metacresol and 3.75g sodium hydrogen phosphate that adding prepares in advance by table 5, add the injection water and be made into 750ml solution, with hydrochloric acid adjust pH to 7.5, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of 70000IU isophane insulin is added pH value is in 2.0 the water for injection, add 43.8mg zinc chloride stirring and dissolving, adding prepares the aqueous solution that contains 31.5g glycerol, 4.9g phenol and metacresol and 0.42g protamine sulfate in advance by table 5, be made into 875ml solution, mix adjust pH to 3.0;
B, 8.75g sodium hydrogen phosphate dissolve with water for injection, add the injection water and are made into 875ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
It is 7.5 qualified to survey pH value and be.
Embodiment 6
Table 6
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 30000IU | ?100000IU | |
| Isophane insulin | ?70000IU | ||
| Glycerol | 12g | ?28g | ?40g |
| Phenol and metacresol | 1.87g | ?4.37g | ?6.2g |
| Zinc chloride | 25.2mg | ?58.4mg | ?83.6mg |
| Sodium hydrogen phosphate | 3.67g | ?8.57g | ?12.2g |
| Protamine sulfate | ?0.31g | ?0.31g | |
| Water for injection | 750ml | ?1750ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 30000IU neutral insulin is joined pH value, add 25.2mg zinc chloride stirring and dissolving again, the aqueous solution that contains 12g glycerol, 1.87g phenol and metacresol and 3.67g sodium hydrogen phosphate that adding prepares in advance by table 6, add the injection water and be made into 750ml solution, with hydrochloric acid adjust pH to 7.2, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of 700000IU isophane insulin is joined pH value is in 2.0 the water for injection, add 58.4mg zinc chloride stirring and dissolving, adding prepares the aqueous solution that contains 28g glycerol, 4.37g phenol and metacresol and 0.31g protamine sulfate in advance by table 6, be made into 875ml solution, mix adjust pH to 2.7;
B, with water for injection dissolving 8.57g sodium hydrogen phosphate, add the injection water and be made into 875ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
It is 7.2 qualified to survey pH value and be.
Three, neutral insulin liquid: isophane insulin solution mixing ratio is the preparation of 5: 5 injection:
Embodiment 7
Table 7
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 50000IU | ?100000IU | |
| Isophane insulin | ?50000IU | ||
| Glycerol | 17.5g | ?17.5g | ?35g |
| Phenol and metacresol | 2.75g | ?2.75g | ?5.5g |
| Zinc chloride | 10.4mg | ?10.5mg | ?20.9mg |
| Sodium hydrogen phosphate | 6g | ?6g | ?12g |
| Protamine sulfate | ?0.15g | ?0.15g | |
| Water for injection | 1250ml | ?1250ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 50000IU neutral insulin is joined pH value, add 10.4mg zinc chloride stirring and dissolving again, the aqueous solution that contains 17.5g glycerol, 2.75g phenol and metacresol and 6g sodium hydrogen phosphate that adding prepares in advance by table 7, be made into 1250ml solution, with hydrochloric acid adjust pH to 6.9, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of 50000IU isophane insulin is joined pH value is in 2.0 the water for injection, add 10.5mg zinc chloride stirring and dissolving, add and prepare the aqueous solution that contains 17.5g glycerol, 2.75g phenol and metacresol and 0.15g protamine sulfate in advance, be made into 625ml solution, mix adjust pH to 2.5;
B, 6g sodium hydrogen phosphate dissolve with water for injection, are made into the 625ml aqueous solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
It is 6.9 qualified to survey pH value and be.
Embodiment 8
Table 8
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 50000IU | ?100000IU | |
| Isophane insulin | ?50000IU | ||
| Glycerol | 22.5g | ?22.5g | ?45g |
| Phenol and metacresol | 3.5g | ?3.5g | ?7g |
| Zinc chloride | 31.3mg | ?31.4mg | ?62.7mg |
| Sodium hydrogen phosphate | 6.25g | ?6.25g | ?12.5g |
| Protamine sulfate | ?0.6g | ?0.6g | |
| Water for injection | 1250ml | ?1250ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 50000IU neutral insulin is joined pH value, add 31.3mg zinc chloride stirring and dissolving again, the aqueous solution that contains 22.5g glycerol, 3.5g phenol and metacresol and 6.25g sodium hydrogen phosphate that adding prepares in advance by table 8, be made into the 1250ml aqueous solution, with hydrochloric acid adjust pH to 7.5, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of 50000IU isophane insulin is joined pH value is in 2.0 the water for injection, add 43.8mg zinc chloride stirring and dissolving, adding prepares the aqueous solution that contains 31.5g glycerol, 4.9g phenol and metacresol and 0.42g protamine sulfate in advance by table 8, be made into 625ml solution, mix adjust pH to 3.0;
B, 6.25g sodium hydrogen phosphate dissolve with water for injection, add the injection water and are made into 625ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
It is 7.5 qualified to survey pH value and be.
Embodiment 9
Table 9
| Prescription | Step (1) | Step (2) | Amount to |
| Neutral insulin | 50000IU | ?100000IU | |
| Isophane insulin | ?50000IU | ||
| Glycerol | 20g | ?20g | ?40g |
| Phenol and metacresol | 3.1g | ?3.1g | ?6.2g |
| Zinc chloride | 41.8mg | ?41.8mg | ?83.6mg |
| Sodium hydrogen phosphate | 6.1g | ?6.1g | ?12.2g |
| Protamine sulfate | ?0.45g | ?0.45g | |
| Water for injection | 1250ml | ?1250ml | ?2500ml |
Preparation method comprises the steps:
(1) preparation neutral insulin liquid:
It is in 2.0 the water for injection that the smart powder of 50000IU neutral insulin is joined pH value, add 41.8mg zinc chloride stirring and dissolving again, the aqueous solution that contains 20g glycerol, 3.1g phenol and metacresol and 6.1g sodium hydrogen phosphate that adding prepares in advance by table 9, be made into the 1250ml aqueous solution, with hydrochloric acid adjust pH to 7.2, through 0.22 μ m membrane filtration degerming, make neutral insulin liquid;
(2) preparation isophane insulin solution:
A, the smart powder of 50000IU isophane insulin is joined pH value is in 2.0 the water for injection, add 41.8mg zinc chloride stirring and dissolving, adding prepares the aqueous solution that contains 20g glycerol, 3.1g phenol and metacresol and 0.45g protamine sulfate in advance by table 9, be made into 625ml solution, mix adjust pH to 2.7;
B, 6.1g sodium hydrogen phosphate dissolve with water for injection, add the injection water and are made into 625ml solution, with 1mol/L hydrochloric acid adjust pH to 8.0;
A and B are mixed, make protaphane beef ampoule;
(3) with neutral insulin liquid and isophane insulin solution mix homogeneously, make protamine zinc insulin injection.
It is 7.2 qualified to survey pH value and be.
Claims (10)
1. protamine zinc insulin injection, comprise insulin, isotonic agent, antiseptic, pH regulator agent, protamine sulfate and water for injection, it is characterized in that: comprise divalent zinc salt in the described water for injection, the concentration of described zinc ion is 0.01～0.04g/100000IU insulin.
2. protamine zinc insulin injection according to claim 1 is characterized in that: described zinc salt is a kind of or its combination in zinc acetate, zinc bromide, zinc chloride, zinc iodide, zinc fluoride, the zinc sulfide.
3. protamine zinc insulin injection according to claim 1 and 2 is characterized in that: described protamine zinc insulin injection comprises following component among the insulin 100000IU:
Isotonic agent 35～45g
Antiseptic 5.5～7g
PH regulator agent 12～12.5g
Protamine sulfate 0.15～0.6g
Surplus is the water for injection that comprises divalent zinc ion, and pH value is 6.9～7.8.
4. protamine zinc insulin injection according to claim 3 is characterized in that: described insulin is Iletin II (Lilly) or bovine insulin; Described isotonic agent is a glycerol; Described antiseptic is phenol and metacresol; Described pH regulator agent is sodium hydrogen phosphate or its crystalline solid.
5. according to the described protamine zinc insulin injection of one of claim 1 to 4, it is characterized in that: described insulin is an isophane insulin.
6. at the preparation method of the described protamine zinc insulin injection of claim 5, comprise the steps:
A, the smart powder of isophane insulin is added pH value is in 1.8～2.2 an amount of water for injection, adds the zinc salt stirring and dissolving, adds the aqueous solution for injection that contains isotonic agent, antiseptic, protamine sulfate, mixes adjust pH to 2.5～3.0.
B, pH regulator agent are dissolved with water for injection, are made into volumetric soiutions, with hydrochloric acid adjust pH to 7.8～8.2.
With A and the mixed isophane insulin solution of making of B.
7. the preparation method of protamine zinc insulin injection according to claim 6 is characterized in that: the solution that steps A, B are made is respectively through 0.2～0.25 μ m membrane filtration degerming.
8. according to the described protamine zinc insulin injection of one of claim 1 to 4, it is characterized in that: described insulin is the mixture that comprises neutral insulin and isophane insulin, wherein, the proportioning of neutral insulin and isophane insulin is 30: 70 or 50: 50.
9. at the preparation method of the described protamine zinc insulin injection of claim 8, comprise the steps:
(1) preparation neutral insulin liquid:
It is in 1.8～2.2 the water for injection that the smart powder of neutral insulin is added pH value, add the zinc salt stirring and dissolving, add the aqueous solution for injection that contains isotonic agent, antiseptic and pH regulator agent, add the injection water and be made into volumetric soiutions, neutral insulin liquid is made in adjust pH to 6.5～7.5;
(2) preparation isophane insulin solution:
A, the smart powder of isophane insulin is added pH value is in 1.8～2.2 the water for injection, adds the zinc salt stirring and dissolving, adds the aqueous solution for injection that contains isotonic agent, antiseptic, protamine sulfate, mixes adjust pH to 2.5～3.0;
B, pH regulator agent are dissolved with water for injection, are made into volumetric soiutions, adjust pH to 7.8～8.2;
A and B are mixed, make protaphane beef ampoule;
(3) neutral insulin liquid and isophane insulin solution is even with 3: 7 or 5: 5 mixed, make protamine zinc insulin injection.
10. the preparation method of protamine zinc insulin injection according to claim 9 is characterized in that: in the described neutral insulin liquid preparation, neutral insulin liquid is through 0.2～0.25 μ m membrane filtration degerming.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2007101734303A CN101219209A (en) | 2007-12-27 | 2007-12-27 | Insulin-protamine zinc injection and method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101734303A CN101219209A (en) | 2007-12-27 | 2007-12-27 | Insulin-protamine zinc injection and method for preparing the same |
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| CN101219209A true CN101219209A (en) | 2008-07-16 |
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| CNA2007101734303A Pending CN101219209A (en) | 2007-12-27 | 2007-12-27 | Insulin-protamine zinc injection and method for preparing the same |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732245A (en) * | 2009-12-30 | 2010-06-16 | 江苏万邦生化医药股份有限公司 | Two-phase isophane zinc recombinant human insulin injection and preparation method thereof |
| CN102188367A (en) * | 2011-01-05 | 2011-09-21 | 山东新时代药业有限公司 | Insulin glargine injecta and preparation method thereof |
| CN102302769A (en) * | 2011-08-15 | 2012-01-04 | 西安交通大学 | Blood-sugar-reducing composition and application thereof |
| CN108114270A (en) * | 2018-02-06 | 2018-06-05 | 美药星（南京）制药有限公司 | A kind of preparation method of insulin aspart parenteral solution |
| CN113384529A (en) * | 2021-07-08 | 2021-09-14 | 北京惠之衡生物科技有限公司 | Asparagus insulin injection and preparation method thereof |
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2007
- 2007-12-27 CN CNA2007101734303A patent/CN101219209A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732245A (en) * | 2009-12-30 | 2010-06-16 | 江苏万邦生化医药股份有限公司 | Two-phase isophane zinc recombinant human insulin injection and preparation method thereof |
| CN102188367A (en) * | 2011-01-05 | 2011-09-21 | 山东新时代药业有限公司 | Insulin glargine injecta and preparation method thereof |
| CN102302769A (en) * | 2011-08-15 | 2012-01-04 | 西安交通大学 | Blood-sugar-reducing composition and application thereof |
| CN108114270A (en) * | 2018-02-06 | 2018-06-05 | 美药星（南京）制药有限公司 | A kind of preparation method of insulin aspart parenteral solution |
| CN108114270B (en) * | 2018-02-06 | 2019-08-20 | 美药星（南京）制药有限公司 | A kind of preparation method of insulin aspart injection |
| CN113384529A (en) * | 2021-07-08 | 2021-09-14 | 北京惠之衡生物科技有限公司 | Asparagus insulin injection and preparation method thereof |
| CN113384529B (en) * | 2021-07-08 | 2021-11-26 | 北京惠之衡生物科技有限公司 | Asparagus insulin injection and preparation method thereof |
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