CN102657851B - Recombinant human interferon alpha2b cream and preparation method thereof - Google Patents
Recombinant human interferon alpha2b cream and preparation method thereof Download PDFInfo
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- CN102657851B CN102657851B CN201210108940.3A CN201210108940A CN102657851B CN 102657851 B CN102657851 B CN 102657851B CN 201210108940 A CN201210108940 A CN 201210108940A CN 102657851 B CN102657851 B CN 102657851B
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Abstract
The invention discloses a recombinant human interferon alpha2b cream, comprising 10-20 mg of recombinant human interferon, 2514g of oil phase substance, 2680g of water phase substance, and 10-60g of pharmaceutical gelatin. The recombinant human interferon alpha2b cream provided by the invention can treat obstinate dermatosis caused by human papilloma virus and herpes simplex virus with good effects. Simultaneously the matrix selected in the invention is a semisolid emulsified by water-oil substances, the matrix has a good affinity for oil and water, so that the recombinant human interferon alpha2b can be well dissolved in the matrix and is convenient for skin to absorb, and the curative effect of the finished pharmaceutical product is further raised, simultaneously exudates on the wound skin can be absorbed, and the matrix is easier to coat, clean and protect skin than greasy matrixes.
Description
Technical field
The present invention relates to drug world, be specifically related to a kind of recombinant human interferon alpha 2 b emulsifiable paste that is used for the treatment of condyloma acuminatum and herpes and preparation method thereof.
Background technology
The herpes labialis that the condyloma acuminatum that human papillomavirus causes and herpes simplex virus cause and genital herpes are all the dermatosis of obstinate type, and existing emulsifiable paste medicine is difficult to its radical cure.Research shows that recombinant human interferon alpha 2 b has good action effect to human papillomavirus and herpes simplex virus, can be used for the treatment of condyloma acuminatum and herpes labialis and genital herpes.
Summary of the invention
The object of this invention is to provide a kind of recombinant human interferon alpha 2 b emulsifiable paste, the herpes that the condyloma acuminatum that this emulsifiable paste causes human papillomavirus and herpes simplex virus cause has good therapeutic effect.
For achieving the above object, the present invention has adopted following technical scheme: a kind of recombinant human interferon alpha 2 b emulsifiable paste, composed of the following components:
Wherein oil phase substance is octadecanol, laurocapram, and three kinds of materials of sorbic acid mix composition; Wherein aqueous phase substance is PVP, Tween 80, and glycerol, four kinds of materials of water for injection mix composition.
Recombinant human interferon alpha 2 b emulsifiable paste provided by the present invention is made up of the pharmagel of recombinant human interferon alpha 2 b and protection recombinant human interferon alpha 2 b activity and the substrate that water-oil phase substance forms.The dermatosis of the obstinate type that recombinant human interferon alpha 2 b can cause human papillomavirus and herpes simplex virus is treated, and action effect is good.
Main active in the present invention is recombinant human interferon alpha 2 b, belongs to protein substance, and it is active relevant with residing environmental factors to its structure.So an important step is exactly to adopt pharmagel as stabilizing agent in this cream preparation method; pharmagel can effectively be protected the activity of recombinant human interferon alpha 2 b; the structure that prevents recombinant human interferon alpha 2 b changes and the impact of environmental factors on its activity, strengthens the curative effect of medicine.
It is the semisolid matrix being formed by the emulsifying of water-oil phase substance that the present invention selects; therefore the substrate forming all has good affinity to oil, water; recombinant human interferon alpha 2 b can be dissolved in substrate preferably; be convenient to the absorption of skin; further increase the curative effect of final drug; also can absorb transudate on skin wound, be easier to coating, clean and protection skin compared with greasing base simultaneously.
Meanwhile, technique scheme is a preparation prescription of the present invention, and a preparation prescription can be made into 1,000 recombinant human interferon alpha 2 b emulsifiable pastes, every dress 5g～10g.As just should add the pharmagel of 0.5g～10g while needing 100ml recombinant human interferon alpha 2 b solution the quality that adds of general pharmagel is with respect to 0.5%～10% of recombinant human interferon alpha 2 b liquor capacity.Recombinant human interferon alpha 2 b 1.0 × 10
8iU: the biological activity that represents interferon is 1.0 × 10
8iu; The addition of pharmagel is 1%～6%, within the scope of this, can have good protective effect to the biological activity of recombinant human interferon alpha 2 b.In addition, the wide material sources of pharmagel and water, oil substances, low price, production cost is low, nontoxic and protective effect is obvious, and the stability of product is strong.Another object of the present invention is to provide the preparation method of this recombinant human interferon alpha 2 b emulsifiable paste, and concrete operation is as follows:
A preparation method for recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 1, comprises following processing step:
S1: the medicine that accurately weighs respective amount according to the dose ratio of each raw material claimed in claim 1 is stand-by, load weighted oil phase substance and aqueous phase substance are carried out to Pressurized-heated sterilization treatment, and then oil phase substance is placed in stirred vessel and constantly and is stirred, be cooled to 80 ℃～90 ℃ and keep temperature constant, again aqueous phase substance added in stirred vessel and constantly stir until biphase material is uniformly mixed the fine and smooth emulsion substrate of rear one-tenth white, being cooled to below 25 ℃;
S2: will be cooled to below 25 ℃ after water for injection dissolving for pharmagel, Pressurized-heated sterilization treatment, then recombinant human interferon alpha 2 b is added in pharmagel solution and dissolves mix homogeneously;
S3: the recombinant human interferon alpha 2 b solution configuring is joined in emulsion substrate, be uniformly mixed rear fill and can make finished product in flexible pipe.
Further scheme is:
Pressurized-heated sterilization treatment described in step S1 and step S2 is all that 0.05～0.1MPa, temperature are to carry out under the condition of 120～130 ℃ at pressure.
Recombinant human interferon alpha 2 b solution described in step S3 and emulsion substrate are cooled to respectively 10～25 ℃ and carry out mixing and stirring again.
Recombinant human interferon alpha 2 b described in step S2 adds and must inject water after pharmagel mix homogeneously and carry out standardize solution processing, and standardize solution needs balance 10～15min after processing, then is cooled to 10～25 ℃.
It is to dissolve in the water for injection of heating that pharmagel described in step S2 dissolves with water for injection.
Simultaneously, in described step S2, the amount adding of pharmagel is to implement with respect to 0.5%～10% of recombinant human interferon alpha 2 b liquor capacity, while being 100ml recombinant human interferon alpha 2 b solution, add the pharmagel of 0.5g～10g, the addition of more preferred pharmagel is 1%～6%, it is that every 1 kilogram of substrate adds 200ml recombinant human interferon alpha 2 b solution that recombinant human interferon alpha 2 b solution described in step S3 joins in emulsion substrate, the protection best results of pharmagel now to recombinant human interferon alpha 2 b activity, the stability of recombinant human interferon alpha 2 b emulsifiable paste is also best.
The present invention is by the effect of oil phase substance and aqueous phase substance, be that oil phase substance is decentralized photo, aqueous phase substance is continuous phase, whole emulsification is that continuous phase is added in decentralized photo, can produce more tiny dispersed phase particles, make recombinant human interferon alpha 2 b be easier to be dissolved in the emulsion substrate after emulsifying, the effective ingredient in the recombinant human interferon alpha 2 b emulsifiable paste that makes to make is kept in balance, and increases curative effect and the stability of recombinant human interferon alpha 2 b emulsifiable paste.The water for injection of heating can accelerate complete swelling and the dissolving of pharmagel simultaneously.In the present invention by recombinant human interferon alpha 2 b solution and the equal balance to 20 ℃ of emulsion substrate, both easy mix homogeneously like this, and now in emulsion substrate the biological activity of recombinant human interferon alpha 2 b also best.
The specific embodiment
Further illustrate technical scheme of the present invention by specific embodiment below.Wherein embodiment
Embodiment 1
Accurately take oil phase substance, i.e. octadecanol, laurocapram (Azone), the mixture 2.514kg of sorbic acid, aqueous phase substance, PVP (PVP), Tween 80 (TWEEN-80), glycerol, the mixture 2.680kg of water for injection, be 0.05～0.1MPa at pressure respectively by oil phase substance and aqueous phase substance, temperature is to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions, and then oil phase substance is placed in stirred vessel and constantly and is stirred, be cooled to 80 ℃～90 ℃ and stirred vessel is placed in and in thermostat water bath, keeps temperature constant, again aqueous phase substance is added in stirred vessel, stir 2h left and right until biphase material is uniformly mixed the fine and smooth emulsion substrate of rear one-tenth white, then be cooled to 20 ℃ stand-by.
Take pharmagel 10.0g and join the water for injection 200ml that is placed in water-bath slight fever, treat that pharmagel dissolves, swelling being evenly placed in Pressurized-heated autoclave, be that 0.05～0.1MPa, temperature are to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions at pressure, then let cool and be cooled to 20 ℃, accurate measuring recombinant human interferon alpha 2 b crude drug 10.0mg (approximately 1.0 × 10
9iu interferon), add in cooled gelatin solution, after being uniformly mixed, be settled to 1L with injection water again, balance 10 minutes.
The interferon solution of the above-mentioned balance to 20 configuring ℃ is slowly joined in the emulsion substrate of continuous stirring, fully stir after 10 minutes fast, then pour fill unit into, ointment is distributed into the finished product that can make in the flexible pipe of having sterilized through fill unit.
Embodiment 2
Accurately take oil phase substance, i.e. octadecanol, laurocapram (Azone), the mixture 2.514kg of sorbic acid, aqueous phase substance, PVP (PVP), Tween 80 (TWEEN-80), glycerol, the mixture 2.680kg of water for injection, be 0.05～0.1MPa at pressure respectively by oil phase substance and aqueous phase substance, temperature is to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions, and then oil phase substance is placed in stirred vessel and constantly and is stirred, be cooled to 80 ℃～90 ℃ and stirred vessel is placed in and in thermostat water bath, keeps temperature constant, again aqueous phase substance is added in stirred vessel, stir 2h left and right until biphase material is uniformly mixed the fine and smooth emulsion substrate of rear one-tenth white, then be cooled to 10 ℃ stand-by.
Take pharmagel 20g and join the water for injection 200ml that is placed in water-bath slight fever, treat that pharmagel dissolves, swelling being evenly placed in Pressurized-heated autoclave, be that 0.05～0.1MPa, temperature are to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions at pressure, then let cool and be cooled to 10 ℃, accurate measuring recombinant human interferon alpha 2 b crude drug 20.0mg (approximately 2.0 × 10
9iu interferon), add in cooled gelatin solution, after being uniformly mixed, be settled to 1L with injection water again, balance 10 minutes.
The interferon solution of the above-mentioned balance to 10 configuring ℃ is slowly joined in the emulsion substrate of continuous stirring, fully stir after 10 minutes fast, then pour fill unit into, ointment is distributed into the finished product that can make in the flexible pipe of having sterilized through fill unit.
Embodiment 3
Accurately take oil phase substance, i.e. octadecanol, laurocapram (Azone), the mixture 2.514kg of sorbic acid, aqueous phase substance, PVP (PVP), Tween 80 (TWEEN-80), glycerol, the mixture 2.680kg of water for injection, be 0.05～0.1MPa at pressure respectively by oil phase substance and aqueous phase substance, temperature is to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions, and then oil phase substance is placed in stirred vessel and constantly and is stirred, be cooled to 80 ℃～90 ℃ and stirred vessel is placed in and in thermostat water bath, keeps temperature constant, again aqueous phase substance is added in stirred vessel, stir 2h left and right until biphase material is uniformly mixed the fine and smooth emulsion substrate of rear one-tenth white, then be cooled to 25 ℃ stand-by.
Take pharmagel 60g and join the water for injection 300ml that is placed in water-bath slight fever, treat that pharmagel dissolves, swelling being evenly placed in Pressurized-heated autoclave, be that 0.05～0.1MPa, temperature are to carry out Pressurized-heated sterilization treatment 30 minutes under 120～130 ℃ of conditions at pressure, then let cool and be cooled to 5 ℃, accurate measuring recombinant human interferon alpha 2 b crude drug 20.0mg (approximately 2.0 × 10
9iu interferon), add in cooled gelatin solution, after being uniformly mixed, be settled to 1L with injection water again, balance 10 minutes.
The interferon solution of the above-mentioned balance to 25 configuring ℃ is slowly joined in the emulsion substrate of continuous stirring, fully stir after 10 minutes fast, then pour fill unit into, ointment is distributed into the finished product that can make in the flexible pipe of having sterilized through fill unit.
In order further to determine the stability of prescription of the present invention and preparation method, respectively embodiment 1-3 to be investigated, result of the test shows: the equal conformance with standard of indices.Detailed results refers to table 1.
4 ℃ of conditions of table 1 recombinant human interferon alpha 2 b (1,000,000 IU/ prop up) emulsifiable paste
The stability test result of lower storage
The using method of recombinant human interferon alpha 2 b emulsifiable paste of the present invention is to be directly applied in affected part, one day four times.Condyloma acuminatum drug treatment is six to eight weeks, or follows the doctor's advice.Herpes labialis and genital herpes continuous use one week.
Clinical test results shows, as shown in table 2, is used for the treatment of genitality herpes by recombinant human interferon alpha 2 b emulsifiable paste, completes altogether 80 cases, and cure rate and effective percentage are respectively 70%, 95%; Be used for the treatment of herpes zoster by recombinant human interferon alpha 2 b emulsifiable paste, complete altogether case 120 examples, cure rate and effective percentage are respectively 51.67%, 81.67%, be used for the treatment of condyloma acuminatum by recombinant human interferon alpha 2 b emulsifiable paste, complete altogether case 50 examples, cure rate and effective percentage are respectively 70.21%, 87.82%.Shortening the only bleb time, there is positive effect effect vesicle extinction time and the time aspect that starts to form a scab.
The Clinical analysis of table 2 recombinant human interferon alpha 2 b emulsifiable paste
Claims (6)
1. a recombinant human interferon alpha 2 b emulsifiable paste, composed of the following components:
Wherein oil phase substance is octadecanol, laurocapram, and three kinds of materials of sorbic acid mix composition;
Wherein aqueous phase substance is PVP, Tween 80, and glycerol, four kinds of materials of water for injection mix composition; Water, oil phase substance emulsifying form semisolid matrix.
2. a preparation method for recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 1, comprises following processing step:
S1: the medicine that accurately weighs respective amount according to the dose ratio of each raw material claimed in claim 1 is stand-by, load weighted oil phase substance and aqueous phase substance are carried out to Pressurized-heated sterilization treatment, and then oil phase substance is placed in stirred vessel and constantly and is stirred, be cooled to 80 ℃～90 ℃ and keep temperature constant, again aqueous phase substance is added in stirred vessel and constantly and stirred 2 hours, till being uniformly mixed to biphase material the emulsion substrate that rear one-tenth white is fine and smooth, be cooled to below 25 ℃;
S2: will be cooled to below 25 ℃ after water for injection dissolving for pharmagel, Pressurized-heated sterilization treatment, then recombinant human interferon alpha 2 b is added in pharmagel solution and dissolves mix homogeneously;
S3: the recombinant human interferon alpha 2 b solution configuring is joined in emulsion substrate, be uniformly mixed rear fill and can make finished product in flexible pipe.
3. the preparation method of recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 2, is characterized in that: the Pressurized-heated sterilization treatment described in step S1 and step S2 is all that 0.05～0.1MPa, temperature are to carry out under the condition of 120～130 ℃ at pressure.
4. the preparation method of recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 2, is characterized in that: the recombinant human interferon alpha 2 b solution described in step S3 and emulsion substrate are cooled to respectively 10～25 ℃ and carry out mixing and stirring again.
5. the preparation method of recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 2, it is characterized in that: the recombinant human interferon alpha 2 b described in step S2 adds and must inject water after pharmagel mix homogeneously and carry out standardize solution processing, standardize solution needs balance 10～15min after processing, then is cooled to 10～25 ℃.
6. the preparation method of recombinant human interferon alpha 2 b emulsifiable paste as claimed in claim 2, is characterized in that: it is to dissolve in the water for injection of heating that the water for injection of the pharmagel described in step S2 dissolves.
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| CN101612114A (en) * | 2009-08-06 | 2009-12-30 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human interferon alpha 2 a2b suppository and preparation method thereof |
| CN101716335A (en) * | 2008-10-09 | 2010-06-02 | 哈药集团生物工程有限公司 | Stable recombinant human interferon ointment |
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| CN1660413A (en) * | 2004-12-30 | 2005-08-31 | 深圳市海王英特龙生物技术股份有限公司 | New aplication of interferon pastille in use for preparing medication of treating recurrent ulcer of oral cavity |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101716335A (en) * | 2008-10-09 | 2010-06-02 | 哈药集团生物工程有限公司 | Stable recombinant human interferon ointment |
| CN101612114A (en) * | 2009-08-06 | 2009-12-30 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human interferon alpha 2 a2b suppository and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 庞传超等.重组人干扰素α-2b 乳膏治疗带状疱疹和生殖器疱疹.《大连医科大学学报》.2003,第25卷(第3期),185-187. |
| 重组人干扰素α-2b 乳膏治疗带状疱疹和生殖器疱疹;庞传超等;《大连医科大学学报》;20030930;第25卷(第3期);185-187 * |
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Denomination of invention: Recombinant human interferon alpha2b cream and preparation method thereof Effective date of registration: 20161101 Granted publication date: 20140618 Pledgee: Huizhou Merchants Bank Hefei Mengcheng road subbranch Pledgor: Anhui Anke Biotechnology (Group) Co., Ltd. Registration number: 2016990000929 |
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Date of cancellation: 20210209 Granted publication date: 20140618 Pledgee: Huizhou Merchants Bank Hefei Mengcheng road subbranch Pledgor: ANHUI ANKE BIOTECHNOLOGY (Group) Co.,Ltd. Registration number: 2016990000929 |