CN103877582B - Compound glycyrrhizin medicinal composition for injection and preparation method thereof - Google Patents
Compound glycyrrhizin medicinal composition for injection and preparation method thereof Download PDFInfo
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- CN103877582B CN103877582B CN201410117923.5A CN201410117923A CN103877582B CN 103877582 B CN103877582 B CN 103877582B CN 201410117923 A CN201410117923 A CN 201410117923A CN 103877582 B CN103877582 B CN 103877582B
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- 239000007924 injection Substances 0.000 title claims abstract description 52
- 238000002347 injection Methods 0.000 title claims abstract description 52
- 150000001875 compounds Chemical class 0.000 title claims abstract description 46
- 239000000203 mixture Substances 0.000 title abstract description 35
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 title abstract description 5
- 229960004949 glycyrrhizic acid Drugs 0.000 title abstract description 5
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 title abstract description 5
- 235000019410 glycyrrhizin Nutrition 0.000 title abstract description 5
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- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title abstract description 4
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- 238000000034 method Methods 0.000 claims abstract description 7
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 154
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- 229930182470 glycoside Natural products 0.000 claims description 131
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- 239000008215 water for injection Substances 0.000 claims description 91
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 78
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- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 claims description 78
- 229950007687 macrogol ester Drugs 0.000 claims description 78
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- 239000004471 Glycine Substances 0.000 claims description 75
- 239000000243 solution Substances 0.000 claims description 63
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
- 229910000831 Steel Inorganic materials 0.000 claims description 23
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- 238000005352 clarification Methods 0.000 description 8
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
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- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 4
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- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
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- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound glycyrrhizin medicinal composition for injection and a preparation method thereof, and belongs to the technical field of medicines. The compound glycyrrhizin medicinal composition for injection, which is prepared by adopting the formula and the process, has a simple formula and does not contain a lyophilized excipient, the prepared product is full in appearance and is a white loose block, the technical biases that the product appearance is maintained by adding dextran and other excipients in the prior art can be overcome, the safety risk caused by adding dextran and other excipients can be reduced, and the safety can be greatly improved; 15-hydroxystearate polyglycol ester is used as a solubilizer, and users unexpectedly discover a higher physiological tolerance, no hemolysis or irritation phenomena and strong solubilizing power of the 15-hydroxystearate polyglycol ester, so that the use safety is improved while the medicine dissolution is guaranteed.
Description
Technical field
The present invention relates to a kind of medicinal composition for injections and preparation technology thereof, particularly a kind of injection use compound glycyrrhizic glycoside pharmaceutical composition and preparation method thereof, belongs to medical art.
Background technology
Compound Glycyrrhizin Injection Concomitant is the earliest by Japanese Development and Production, and imported medicine commodity are called " U.S. energy ".Find that the easy crystallization of glycyrrhiza compound acid injection causes the stability of injection bad in actual applications, therefore be made into powder injection formulation to improve the stability of preparation.
Application number be 200810115716.0 Chinese patent disclose a kind of powder injection of compound glycyrrhizic acid glycosides and preparation method thereof, this patent prescription contains glycyrrhizic glycoside (or glycyrrhizic glycoside mono-ammonium), glycine, cysteine hydrochloride, dextran, anhydrous sodium sulfite and calcium disodium edetate.Use dextran as carrier in this prescription, but it is well-known, dextran is even anaphylaxis, as urticaria, skin pruritus, heating, Nausea and vomiting, pant, arthralgia, hemorrhage etc., extremely individual other has blood pressure drops, dyspnea and the situation such as uncomfortable in chest to occur, clinical practice exists certain potential safety hazard.
Application number be 200710028444.6 Chinese patent disclose a kind of dried frozen aquatic products prescription containing glycyrrhizic glycoside and preparation method thereof, containing glycyrrhizic glycoside (or glycyrrhizic glycoside mono-ammonium), glycine, cysteine hydrochloride, anhydrous sodium sulfite, calcium disodium edetate and sodium hydroxide in this patent prescription.Cosolvent is made with sodium hydroxide in this prescription, but sodium hydroxide Chang Zuowei pH adjusting agent, limited as its solubilizing effect of solubilizing agent.In addition, also use calcium disodium edetate in prescription as chelating agent, but due to calcium disodium edetate harmful, the excessive renal cells that causes of dosage damages, and causes acute failure; Can be there is complexation syndrome in long-time heavy dose of medication, therefore need in use strictly to control consumption, avoids bringing potential safety hazard.
Therefore, research and develop that a kind of outward appearance is good, steady quality, solubility and compatibility stability are good and the injection use compound glycyrrhizic glycoside injectable powder that production cost is lower, have great importance, the present invention meets such demand.
Summary of the invention
For the problems referred to above, the invention provides a kind of new injection use compound glycyrrhizic glycoside pharmaceutical composition and preparation method thereof, prescription is simple, and technique is easy to operation, and the product appearance prepared is full, steady quality, solubility and compatibility stability better.
For achieving the above object, injection use compound glycyrrhizic glycoside pharmaceutical composition provided by the invention, is made up of glycyrrhizic glycoside, glycine, L-cysteine hydrochloride, sodium sulfite and 15-hydroxy stearic acid macrogol ester.
Injection use compound glycyrrhizic glycoside pharmaceutical composition of the present invention, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg ~ 100mg, glycine 200mg ~ 1000mg, L-cysteine hydrochloride 10mg ~ 50mg, sodium sulfite 8mg ~ 40mg, 15-hydroxy stearic acid macrogol ester 50mg ~ 250mg.
Preferably, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg ~ 80mg, glycine 400mg ~ 800mg, L-cysteine hydrochloride 20mg ~ 40mg, sodium sulfite 16mg ~ 32mg, 15-hydroxy stearic acid macrogol ester 100mg ~ 200mg.
Preferred, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg, glycine 200mg, L-cysteine hydrochloride 10mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 50mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg, glycine 200mg, L-cysteine hydrochloride 10mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 250mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg, glycine 200mg, L-cysteine hydrochloride 10mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 50mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg, glycine 200mg, L-cysteine hydrochloride 10mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 250mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 100mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 200mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 100mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 200mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 50mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 100mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 24mg, 15-hydroxy stearic acid macrogol ester 150mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 200mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 250mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 80mg, glycine 800mg, L-cysteine hydrochloride 40mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 100mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 80mg, glycine 800mg, L-cysteine hydrochloride 40mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 200mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 80mg, glycine 800mg, L-cysteine hydrochloride 40mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 100mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 80mg, glycine 800mg, L-cysteine hydrochloride 40mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 200mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 100mg, glycine 1000mg, L-cysteine hydrochloride 50mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 50mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 100mg, glycine 1000mg, L-cysteine hydrochloride 50mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 250mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 100mg, glycine 1000mg, L-cysteine hydrochloride 50mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 50mg.
Or the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 100mg, glycine 1000mg, L-cysteine hydrochloride 50mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 250mg.
Present invention also offers a kind of preparation method of injection use compound glycyrrhizic glycoside pharmaceutical composition, the method comprises the following steps: add preparation total amount 70% water for injection in rustless steel container, control the temperature of water for injection at 45 DEG C ~ 60 DEG C, add the sodium sulfite of recipe quantity, 15-hydroxy stearic acid macrogol ester successively, stir and make to dissolve completely; Add glycyrrhizic glycoside, stir and make to dissolve completely; Add glycine, stir and make to dissolve completely; Add L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
The injection use compound glycyrrhizic glycoside prepared by the present invention is had the following advantages:
(1) the present invention uses 15-hydroxy stearic acid macrogol ester as solubilizing agent, is surprised to find that it has higher physiological tolerance, even if can also painless administration when high concentration, without haemolysis with stimulate phenomenon to occur, safety be better; And solubilising power is comparatively strong, can guarantee that medicine redissolves fast and continually and steadily, improves product quality;
(2) lyophilizing excipient is not used in prescription, prepared product appearance is still full, in white loose block, overcome in prior art and need to add the excipient such as dextran to maintain the technology prejudice of product design, reduce the security risk brought owing to adding the excipient such as dextran, safety improves greatly simultaneously.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but not limitation of the present invention, and the equivalent replacement of all any this areas done according to the disclosure of invention, all belongs to protection scope of the present invention.
Embodiment 1 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 20g |
| Glycine | 200g |
| L-cysteine hydrochloride | 10g |
| Sodium sulfite | 8g |
| 15-hydroxy stearic acid macrogol ester | 50g |
| Water for injection | 1000ml |
Preparation technology: add the water for injection of 700ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 8g sodium sulfite, 50g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 20g glycyrrhizic glycoside, stir and make to dissolve completely; Add 200g glycine, stir and make to dissolve completely; Add 10g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 2 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 20g |
| Glycine | 200g |
| L-cysteine hydrochloride | 10g |
| Sodium sulfite | 8g |
| 15-hydroxy stearic acid macrogol ester | 250g |
| Water for injection | 1000ml |
Preparation technology: add the water for injection of 700ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 8g sodium sulfite, 250g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 20g glycyrrhizic glycoside, stir and make to dissolve completely; Add 200g glycine, stir and make to dissolve completely; Add 10g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 3 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 20g |
| Glycine | 200g |
| L-cysteine hydrochloride | 10g |
| Sodium sulfite | 40g |
| 15-hydroxy stearic acid macrogol ester | 50g |
| Water for injection | 1000ml |
Preparation technology: add the water for injection of 700ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 40g sodium sulfite, 50g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 20g glycyrrhizic glycoside, stir and make to dissolve completely; Add 200g glycine, stir and make to dissolve completely; Add 10g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 4 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 20g |
| Glycine | 200g |
| L-cysteine hydrochloride | 10g |
| Sodium sulfite | 40g |
| 15-hydroxy stearic acid macrogol ester | 250g |
| Water for injection | 1000ml |
Preparation technology: add the water for injection of 700ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 40g sodium sulfite, 250g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 20g glycyrrhizic glycoside, stir and make to dissolve completely; Add 200g glycine, stir and make to dissolve completely; Add 10g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 5 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 40g |
| Glycine | 400g |
| L-cysteine hydrochloride | 20g |
| Sodium sulfite | 16g |
| 15-hydroxy stearic acid macrogol ester | 100g |
| Water for injection | 2000ml |
Preparation technology: add the water for injection of 1400ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 16g sodium sulfite, 100g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 40g glycyrrhizic glycoside, stir and make to dissolve completely; Add 400g glycine, stir and make to dissolve completely; Add 20g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 6 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 40g |
| Glycine | 400g |
| L-cysteine hydrochloride | 20g |
| Sodium sulfite | 16g |
| 15-hydroxy stearic acid macrogol ester | 200g |
| Water for injection | 2000ml |
Preparation technology: add the water for injection of 1400ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 16g sodium sulfite, 200g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 40g glycyrrhizic glycoside, stir and make to dissolve completely; Add 400g glycine, stir and make to dissolve completely; Add 20g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 7 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 40g |
| Glycine | 400g |
| L-cysteine hydrochloride | 20g |
| Sodium sulfite | 32g |
| 15-hydroxy stearic acid macrogol ester | 100g |
| Water for injection | 2000ml |
Preparation technology: add the water for injection of 1400ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 32g sodium sulfite, 100g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 40g glycyrrhizic glycoside, stir and make to dissolve completely; Add 400g glycine, stir and make to dissolve completely; Add 20g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 8 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 40g |
| Glycine | 400g |
| L-cysteine hydrochloride | 20g |
| Sodium sulfite | 32g |
| 15-hydroxy stearic acid macrogol ester | 200g |
| Water for injection | 2000ml |
Preparation technology: add the water for injection of 1400ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 32g sodium sulfite, 200g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 40g glycyrrhizic glycoside, stir and make to dissolve completely; Add 400g glycine, stir and make to dissolve completely; Add 20g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 9 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 60g |
| Glycine | 600g |
| L-cysteine hydrochloride | 30g |
| Sodium sulfite | 8g |
| 15-hydroxy stearic acid macrogol ester | 50g |
| Water for injection | 3000ml |
Preparation technology: add the water for injection of 2100ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 8g sodium sulfite, 50g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 60g glycyrrhizic glycoside, stir and make to dissolve completely; Add 600g glycine, stir and make to dissolve completely; Add 30g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 10 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 60g |
| Glycine | 600g |
| L-cysteine hydrochloride | 30g |
| Sodium sulfite | 16g |
| 15-hydroxy stearic acid macrogol ester | 100g |
| Water for injection | 3000ml |
Preparation technology: add the water for injection of 2100ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 16g sodium sulfite, 100g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 60g glycyrrhizic glycoside, stir and make to dissolve completely; Add 600g glycine, stir and make to dissolve completely; Add 30g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 11 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 60g |
| Glycine | 600g |
| L-cysteine hydrochloride | 30g |
| Sodium sulfite | 24g |
| 15-hydroxy stearic acid macrogol ester | 150g |
| Water for injection | 3000ml |
Preparation technology: add the water for injection of 2100ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 24g sodium sulfite, 150g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 60g glycyrrhizic glycoside, stir and make to dissolve completely; Add 600g glycine, stir and make to dissolve completely; Add 30g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 12 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 60g |
| Glycine | 600g |
| L-cysteine hydrochloride | 30g |
| Sodium sulfite | 32g |
| 15-hydroxy stearic acid macrogol ester | 200g |
| Water for injection | 3000ml |
Preparation technology: add the water for injection of 2100ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 32g sodium sulfite, 200g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 60g glycyrrhizic glycoside, stir and make to dissolve completely; Add 600g glycine, stir and make to dissolve completely; Add 30g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 13 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 60g |
| Glycine | 600g |
| L-cysteine hydrochloride | 30g |
| Sodium sulfite | 40g |
| 15-hydroxy stearic acid macrogol ester | 250g |
| Water for injection | 3000ml |
Preparation technology: add the water for injection of 2100ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 40g sodium sulfite, 250g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 60g glycyrrhizic glycoside, stir and make to dissolve completely; Add 600g glycine, stir and make to dissolve completely; Add 30g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 14 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 80g |
| Glycine | 800g |
| L-cysteine hydrochloride | 40g |
| Sodium sulfite | 16g |
| 15-hydroxy stearic acid macrogol ester | 100g |
| Water for injection | 4000ml |
Preparation technology: add the water for injection of 2800ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 16g sodium sulfite, 100g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 80g glycyrrhizic glycoside, stir and make to dissolve completely; Add 800g glycine, stir and make to dissolve completely; Add 40g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 15 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 80g |
| Glycine | 800g |
| L-cysteine hydrochloride | 40g |
| Sodium sulfite | 16g |
| 15-hydroxy stearic acid macrogol ester | 200g |
| Water for injection | 4000ml |
Preparation technology: add the water for injection of 2800ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 16g sodium sulfite, 200g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 80g glycyrrhizic glycoside, stir and make to dissolve completely; Add 800g glycine, stir and make to dissolve completely; Add 40g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 16 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 80g |
| Glycine | 800g |
| L-cysteine hydrochloride | 40g |
| Sodium sulfite | 32g |
| 15-hydroxy stearic acid macrogol ester | 100g |
| Water for injection | 4000ml |
Preparation technology: add the water for injection of 2800ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 32g sodium sulfite, 100g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 80g glycyrrhizic glycoside, stir and make to dissolve completely; Add 800g glycine, stir and make to dissolve completely; Add 40g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 17 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 80g |
| Glycine | 800g |
| L-cysteine hydrochloride | 40g |
| Sodium sulfite | 32g |
| 15-hydroxy stearic acid macrogol ester | 200g |
| Water for injection | 4000ml |
Preparation technology: add the water for injection of 2800ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 32g sodium sulfite, 200g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 80g glycyrrhizic glycoside, stir and make to dissolve completely; Add 800g glycine, stir and make to dissolve completely; Add 40g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 18 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 100g |
| Glycine | 1000g |
| L-cysteine hydrochloride | 50g |
| Sodium sulfite | 8g |
| 15-hydroxy stearic acid macrogol ester | 50g |
| Water for injection | 5000ml |
Embodiment 19 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 100g |
| Glycine | 1000g |
| L-cysteine hydrochloride | 50g |
| Sodium sulfite | 8g |
| 15-hydroxy stearic acid macrogol ester | 250g |
| Water for injection | 5000ml |
Preparation technology: add the water for injection of 3500ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 8g sodium sulfite, 250g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 100g glycyrrhizic glycoside, stir and make to dissolve completely; Add 1000g glycine, stir and make to dissolve completely; Add 50g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 20 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 100g |
| Glycine | 1000g |
| L-cysteine hydrochloride | 50g |
| Sodium sulfite | 40g |
| 15-hydroxy stearic acid macrogol ester | 50g |
| Water for injection | 5000ml |
Preparation technology: add the water for injection of 3500ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 40g sodium sulfite, 50g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 100g glycyrrhizic glycoside, stir and make to dissolve completely; Add 1000g glycine, stir and make to dissolve completely; Add 50g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Embodiment 21 injection use compound glycyrrhizic glycoside prescription (in 1000, unit: g)
| Glycyrrhizic glycoside | 100g |
| Glycine | 1000g |
| L-cysteine hydrochloride | 50g |
| Sodium sulfite | 40g |
| 15-hydroxy stearic acid macrogol ester | 250g |
| Water for injection | 5000ml |
Preparation technology: add the water for injection of 3500ml in rustless steel container, the temperature controlling water for injection, at 45 DEG C ~ 60 DEG C, adds 40g sodium sulfite, 250g15-hydroxy stearic acid macrogol ester successively, stirs and makes to dissolve completely; Add 100g glycyrrhizic glycoside, stir and make to dissolve completely; Add 1000g glycine, stir and make to dissolve completely; Add 50g L-cysteine hydrochloride, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
Comparative formulation 1: prepare Comparative formulation 1 sample, specification according to the prescription of " 1.1 formulation and technology 1 " in Chinese patent (application number 200810115716.0) embodiment 1 and technique: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg.
Comparative formulation 2: prepare Comparative formulation 2 sample, specification according to the prescription of embodiment 1 in Chinese patent (application number 200710028444.6) and technique: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg.
Test example 1 quality research is tested
Get sample and Comparative formulation 1, Comparative formulation 2 sample prepared by the embodiment of the present invention 1,5,17, under being placed in the condition of temperature 40 DEG C ± 2 DEG C, carry out accelerated test, respectively at the 1st, 2,3, sampling in June, investigate indices situation of change.Result of the test is as shown in the table.
Table 1 embodiment of the present invention and Comparative formulation accelerated test result ()
Table 2 embodiment of the present invention and Comparative formulation accelerated test result (two)
Result shows, after embodiment of the present invention sample, Comparative formulation 1 sample, Comparative formulation 2 sample place 6 months under acceleration conditions, indices, compared with 0 month, all significant change does not occur.Embodiment of the present invention sample, compared with Comparative formulation 1, Comparative formulation 2 sample, outward appearance, acid-base value, clarity and color, visible foreign matters and content's index all conforms with the regulations, each other no difference of science of statistics; But on related substance and loss on drying index, embodiment of the present invention sample is all significantly less than Comparative formulation 1, Comparative formulation 2 sample under the same terms.
As can be seen from the above results, embodiment of the present invention sample is all obviously better than Comparative formulation sample in loss on drying, related substance etc., and the product prepared according to technical scheme of the present invention comparatively Comparative formulation sample quality significantly improves.
Test example 2 is redissolved and is tested
Get the embodiment of the present invention 1,5,11,17,21 sample and Comparative formulation 1, each 5 of Comparative formulation 2 sample, often prop up and add the redissolution of appropriate water for injection, make the solution containing glycyrrhizic glycoside 20mg in every 1ml, observe and record the clarification phenomenon of dissolving the required time completely and redissolving rear solution.
The redissolution speed of table 3 embodiment of the present invention and Comparative formulation and clarity of solution
| Sample | Dissolution time/S | Clarity of solution |
| Embodiment 1 | About 17S | Clarification |
| Embodiment 5 | About 15S | Clarification |
| Embodiment 11 | About 16S | Clarification |
| Embodiment 17 | About 17S | Clarification |
| Embodiment 21 | About 18S | Clarification |
| Comparative formulation 1 | About 45S | Clarification |
| Comparative formulation 2 | About 40S | Clarification |
As can be seen from the above results, when embodiment of the present invention sample sterilized water for injection redissolves, all dissolve completely about 17 seconds, obtain settled solution, and Comparative formulation 1 sample just dissolves completely about 45 seconds, obtain settled solution, Comparative formulation 2 sample dissolves completely about 40 seconds, obtains settled solution.Illustrate that embodiment of the present invention sample is compared with Comparative formulation 1, Comparative formulation 2, solubility is better.
Test example 3 compatibility mechanism
Get sample and Comparative formulation 1, each 2 of Comparative formulation 2 sample of the embodiment of the present invention 1,5,17 preparation, be 2mg/ml by the concentration that 5% glucose injection and 0.9% sodium chloride injection are diluted to glycyrrhizic glycoside respectively, place under room temperature, sample respectively at 0h, 4h, 8h, 12h, 24h and measure, investigate the mass change situation of this product in 5% glucose injection and 0.9% sodium chloride injection.Result of the test is in table 4 and table 5.
The compatibility mechanism result of table 4 and 5% glucose injection
The compatibility mechanism result of table 5 and 0.9% sodium chloride injection
Compatibility mechanism result shows, after embodiment of the present invention sample and 5% glucose injection and 0.9% sodium chloride injection compatibility, place under room temperature after 24 hours, pH value, glycyrrhizic glycoside content, L-CYSTEAMINE HCL acid content, Glycine Levels and related substance all do not have significant change, and in 24 hours, quality is highly stable; Comparative formulation 1 and Comparative formulation 2 sample are with 5% glucose injection and 0.9% sodium chloride injection compatibility and after placing 24 hours, the pH value of medicinal liquid, glycyrrhizic glycoside content, L-CYSTEAMINE HCL acid content, Glycine Levels do not change substantially, but related substance obviously increases, and be far longer than the related substance amount of embodiment of the present invention sample.Visible, the compatibility stability of embodiment of the present invention sample and 5% glucose injection and 0.9% sodium chloride injection is better.
Test example 4 safety testing
By hemolytic and Local irritation study, the safety of injection use compound glycyrrhizic glycoside pharmaceutical composition prepared by the present invention is verified.
The preparation of need testing solution: embodiment 1, embodiment 5, embodiment 17 sample are mixed with the solution that glycyrrhizic glycoside concentration is 2mg/ml respectively with 0.9% sodium chloride injection, as need testing solution, for subsequent use.
(1) haemolysis and agglutination test
The preparation of 2% red blood cell suspension: get healthy rabbits blood, put into conical flask, stir blood with Glass rod, to remove Fibrinogen, makes into defibrinated blood.Add 0.9% sodium chloride solution about 10 times amount, shake up, per minute 1000 ~ 1500 leave the heart 15 minutes, removing supernatant, and the erythrocyte of precipitation washs 2 ~ 3 times as stated above with 0.9% sodium chloride solution again, to the not aobvious redness of supernatant.The erythrocyte of gained is made the suspension of 2% with 0.9% sodium chloride solution, be for experiment.
Get 11, cleaned glass test tube and number, wherein 1, No. 2 pipe is embodiment 1 sample test sample pipe, 3, No. 4 pipes are embodiment 5 sample test sample pipe, 5, No. 6 pipes are embodiment 17 sample test sample pipe, No. 7 pipes are negative control pipe, and No. 8 pipes are positive control pipe, and No. 9 pipes are embodiment 1 test sample control tube, No. 10 pipes are embodiment 5 test sample control tube, and No. 11 pipes are embodiment 17 test sample control tube.Add 2% red cell suspension, 0.9% sodium chloride solution, distilled water shown according to the form below successively, after mixing, put immediately in the calorstat of 37 DEG C ± 0.5 DEG C and carry out incubation, after 3 hours, observe haemolysis and aggregation.
Table 6 haemolysis and agglutination test scheme
The haemolysis situation of each pipe of perusal, found that, namely occurs haemolysis after positive control pipe (No. 8 pipes) adds distilled water in 15 minutes; 9 ~ No. 11 pipes are colourless clear liquid, and 1 ~ No. 7 pipe erythrocyte sinks, and supernatant achromatism and clarity, manages almost zero difference with 9 ~ No. 11, shows that the embodiment of the present invention 1,5,17 sample occurs without haemolysis; Reversed 3 times gently by 1 ~ No. 7 pipe, visible red cell evenly scatters, and proves to occur without red blood cell condensation.Result shows: the injection use compound glycyrrhizic glycoside that the embodiment of the present invention 1,5,17 provides to family's rabbit erythrocyte without haemolysis and cause cohesion.(2) irritation test
Get health, ear edge not damaged rabbit 24, be divided into A, B, C, D tetra-groups at random, often organize 6.Wherein, A group: embodiment 1 sample need testing solution, B group: embodiment 5 sample need testing solution, C group: embodiment 17 sample need testing solution, D group: 0.9% sodium chloride injection matched group.To be in the intravenous drip of rabbit ear edge above-mentioned A, B, C, D tetra-groups of injection with aseptic manipulation respectively.Through multiple dosing, perusal phenomenon is: when vein slowly instils, A, B, C group rabbit is all without struggle reaction, and medication local has no the symptom such as congested, red and swollen, and blood vessel lines is very clear, and surrounding tissue is without obvious edema.Histopathologic slide's check result is visible: auricular vein is without endothelial denudation, and Endothelial Structure is complete, without thrombosis, also has no other extremely, compares no significant difference with 0.9% sodium chloride injection group (D group).Result shows, injection use compound glycyrrhizic glycoside pharmaceutical composition of the present invention is to blood vessel nonirritant.
Known by above-mentioned result of the test, the injection use compound glycyrrhizic glycoside pharmaceutical composition adopting prescription of the present invention and technique to prepare, prescription is simple, do not use any lyophilizing excipient, but prepared product appearance is still full, in white loose block, overcome in prior art and need to add the excipient such as dextran to maintain the technology prejudice of product design, reduce the security risk brought owing to adding the excipient such as dextran, safety improves greatly simultaneously; The present invention uses 15-hydroxy stearic acid macrogol ester as solubilizing agent, is surprised to find that it has higher physiological tolerance, occur, and solubilising power is comparatively strong, while guaranteeing drug-eluting, improve safety in utilization without haemolysis and stimulation phenomenon.The constant product quality adopting technical scheme of the present invention to prepare, redissolve rapidly, compatibility stability is good, compared with prior art, has outstanding substantive distinguishing features and significant progressive.
Claims (9)
1. an injection use compound glycyrrhizic glycoside pharmaceutical composition, is characterized in that, this pharmaceutical composition is made up of glycyrrhizic glycoside, glycine, L-cysteine hydrochloride, sodium sulfite and 15-hydroxy stearic acid macrogol ester.
2. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 1, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg ~ 100mg, glycine 200mg ~ 1000mg, L-cysteine hydrochloride 10mg ~ 50mg, sodium sulfite 8mg ~ 40mg, 15-hydroxy stearic acid macrogol ester 50mg ~ 250mg.
3. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg ~ 80mg, glycine 400mg ~ 800mg, L-cysteine hydrochloride 20mg ~ 40mg, sodium sulfite 16mg ~ 32mg, 15-hydroxy stearic acid macrogol ester 100mg ~ 200mg.
4. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 20mg, glycine 200mg, L-cysteine hydrochloride 10mg, sodium sulfite 8mg, 15-hydroxy stearic acid macrogol ester 50mg.
5. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 40mg, glycine 400mg, L-cysteine hydrochloride 20mg, sodium sulfite 16mg, 15-hydroxy stearic acid macrogol ester 100mg.
6. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 60mg, glycine 600mg, L-cysteine hydrochloride 30mg, sodium sulfite 24mg, 15-hydroxy stearic acid macrogol ester 150mg.
7. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 80mg, glycine 800mg, L-cysteine hydrochloride 40mg, sodium sulfite 32mg, 15-hydroxy stearic acid macrogol ester 200mg.
8. injection use compound glycyrrhizic glycoside pharmaceutical composition according to claim 2, it is characterized in that, the pharmaceutical composition of per unit preparation is composed of the following components: glycyrrhizic glycoside 100mg, glycine 1000mg, L-cysteine hydrochloride 50mg, sodium sulfite 40mg, 15-hydroxy stearic acid macrogol ester 250mg.
9. the preparation method of the injection use compound glycyrrhizic glycoside pharmaceutical composition described in an any one of claim 1 ~ 8, it is characterized in that, the method comprises the following steps: add preparation total amount 70% water for injection in rustless steel container, control the temperature of water for injection at 45 DEG C ~ 60 DEG C, add the sodium sulfite of recipe quantity, 15-hydroxy stearic acid macrogol ester successively, be stirred to dissolve; Add the glycyrrhizic glycoside of recipe quantity, stir and make to dissolve completely; Add the glycine of recipe quantity, stir and make to dissolve completely; Add the L-cysteine hydrochloride of recipe quantity, stir and make to dissolve completely; Measure the pH value of solution, with 10% sodium hydroxide solution adjust pH to 6.2 ~ 6.4; Add dosing amount 0.1%(w/v) medicinal charcoal, 45 DEG C ~ 60 DEG C insulation absorption 15 minutes, stir, coarse filtration takes off charcoal while hot; Add to the full amount of water for injection, after stirring, measure pH value range and control between 6.0 ~ 7.5, fine straining, fill, half tamponade, lyophilization, rolls lid, lamp inspection, labeling, packaging.
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| CN101317851A (en) * | 2007-06-06 | 2008-12-10 | 广州名冠医药科技有限公司 | Freeze drying prescription containing glycyrrhizin and preparation method thereof |
| CN101791295A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Compound monoammonium glycyrrhizinate S pharmaceutical composition and method for preparing frozen powder injection |
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| CN101317851A (en) * | 2007-06-06 | 2008-12-10 | 广州名冠医药科技有限公司 | Freeze drying prescription containing glycyrrhizin and preparation method thereof |
| CN101791295A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Compound monoammonium glycyrrhizinate S pharmaceutical composition and method for preparing frozen powder injection |
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| 几种注射用表面活性剂的质量标准及安全性概述;易红等;《中国实验方剂学杂志》;20100131;第16卷(第1期);第115-119页 * |
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Address after: 611731 Chengdu province high tech Zone, west of the source road, No. 8, No. Patentee after: CHENGDU EASTON BIOPHARMACEUTICALS CO., LTD. Address before: 611731 Chengdu province high tech Zone, west of the source road, No. 8, No. Patentee before: Chengdu Easton Pharmaceutical Co., Ltd. |