Patent Application
20080009453
According to a first embodiment of the pharmaceutical composition of the present invention, a process of making polydatin aqueous solution for injection is provided.
According to a first exemplary illustration of the first embodiment, a process of making an aqueous solution for injection is described, wherein the aqueous solution has a composition comprising a quantity of polydatin, a quantity of NaOH aqueous solution at pH 8.5 and a quantity of 3.6% NaCl aqueous solution. According to the composition of the first exemplary illustration, the quantity of polydatin is 40 g, the quantity of NaOH solution is 8 L, and the quantity of 3.6% NaCl is used for adjusting the total volume of the composition into a 10 L solution, wherein the composition of the first exemplary illustration is divided into 1000 unit.
The process of making an aqueous solution for injection comprises the steps of dissolving 40 g polydatin in 8 L NaOH aqueous solution at pH 8.5; adding a quantity of NaCl until the total volume is 9.8 L; adjusting the pH to 8.5 and adding NaCl aqueous solution until the total volume is 10 L; filtering using 0.22 μm microfilter membrane; and dividing the solution into 1000 units and keeping in ampoules or bottles.
According to a second exemplary illustration of the first embodiment, a process of making an aqueous solution for injection is described, wherein the aqueous solution has a composition comprising a quantity of polydatin, a quantity of NaOH aqueous solution at pH 8.5, a quantity of propandiol, a quantity of Tween 80, and a quantity of 3.6% NaCl aqueous solution. According to the composition of the first exemplary illustration, the quantity of polydatin is 80 g, the quantity of NaOH solution is 6 L, the quantity of propandiol is 2 L, the quantity of Tween 80 is 50 ml, and the quantity of 3.6% NaCl is used for adjusting the total volume of the composition into a 10 L solution, wherein the composition of the first exemplary illustration is divided into 1000 unit.
The process of making an aqueous solution for injection in the embodiment 1-2 comprises the steps of dissolving 40 g polydatin in 2 L propandiol solution; adding 50 ml Tween 80 and NaOH aqueous solution respectively and mixing; adding a quantity of 3.6% NaCl until the total volume is 9.8 L; adjusting the pH to 8.5 and adding NaCl aqueous solution until the total volume is 10 L; filtering using 0.22 μm microfilter membrane; and dividing the solution into 1000 units and keeping in ampoules or bottles.
According to a third exemplary illustration of the first embodiment, a process of making an aqueous solution for injection is described, wherein the aqueous solution has a composition comprising a quantity of polydatin, a quantity of anhydrous alcohol, propandiol, and a quantity of sodium carbon. According to the composition of the third exemplary illustration, the quantity of polydatin is 100 g, the quantity of anhydrous alcohol is 2250 ml, the quantity of propandiol is 1000 ml, and the quantity of sodium carbonate is used for adjusting the total volume of the aqueous solution into 5000 ml. The aqueous solution in the embodiment 1-3 is diluted 25 to 50 times by 0.9% sodium fluoride or 5% glucose injection solution for administration.
The process of making an aqueous solution for injection in the embodiment 1-3 comprises the steps of dissolving 20 g polydatin in 450 ml anhydrous alcohol; adding 100 ml buffer solution and mixing by ultrasound or stirring for 2 to 5 minutes such that the polydatin is dissolved; adding 200 ml propandiol and the remaining buffer solution until the total volume is 1 L; filtering using 0.22 μm microfilter membrane; and refilling nitrogen and dividing the solution into 1000 units which are kept in brown ampoules or bottles. The buffer solution is prepared by mixing one unit of 0.1 mol/L sodium carbonate and nine units of 0.1 mol/L sodium hydrocarbonate.
A process of making a cool dry powder of polydatin for injection.
A process of making a polydatin solution is illustrated in embodiment 2-1. The process of making a polydatin solution in the embodiment 2-1 comprises the steps of dissolving 40 g polydatin in 8 L pH 8.5 NaOH aqueous solution; adding a quantity of 5% aqueous manitol solution until the total volume is 9.8 L; adjusting the pH to 8.5 and adding 3.6% NaCl aqueous solution until the total volume is 10 L; filtering using 0.22 um microfilter membrane; and dividing the solution into 1000 units and keeping in vial for dry powder.
A process of freeze dry is also illustrated in the embodiment 2-1, comprising the step of obtaining the solution obtained from the process of making a polydatin solution, and placing the solution in a freeze dry condition with a temperature at −35° C. such that the solution is kept in −30° C. for 3 hours; vacuum pumping at condensation temperature at −40° C. and increasing the temperature to 40° C. gradually such that the frozen solution is increased gradually; drying the frozen solution and that the freeze dry product is obtained. The product can then be packed and pressed with piston, enclosed and labeled as a polydatin injection powder. The powder is adapted for dissolving in physiological saline for injection use.
A process of making a polydatin solution is illustrated in embodiment 2-2. The process of making a polydatin solution in the embodiment 2-2 comprises the steps of dissolving 80 g polydatin in 8 L pH 9.5 NaOH aqueous solution; adding a quantity of 5% aqueous manitol solution until the total volume is 9.8 L; adjusting the pH to 8.5 and adding 3.6% NaCl aqueous solution until the total volume is 10 L; filtering using 0.22 μm microfilter membrane; and dividing the solution into 1000 units and keeping in vial for freeze dry powder.
A process of freeze dry is also illustrated in the embodiment 2-2, comprising the step of obtaining the solution obtained from the process of making a polydatin solution, and placing the solution in a freeze dry condition with a temperature at −30° C. such that the solution is kept in −30° C. for 3 hours; vacuum pumping at condensation temperature at −40° C. and increasing the temperature to 40° C. gradually such that the frozen solution is increased gradually; drying the frozen solution and that the freeze dry product is obtained. The product can then be packed and pressed with piston, enclosed and labeled as a polydatin injection powder. The powder is adapted for dissolving in physiological saline for injection use.
A process of making an injection solution of the present invention is illustrated in the embodiment 2-2, comprising the steps of mixing 2 L propandiol and 500 ml 0.5% hydrochloric acid; adding a predetermined quantity of physiology saline such that the total volume is 10 L, filtering using 0.22 μm microfilter membrane; and dividing the solution into 1000 units and keeping in vial. Each of the vials comprises 10 ml of injection solution.
A package comprising a 10 ml injection solution and a unit of freeze dry powder is preferred such that the freeze dry powder is capable of dissolving in the injection solution for injection.
A process of making a composition of polydatin in tablet form. 1000 tablet each having a composition of 50 mg polydatin are prepared according to the routine making process, and that the composition of polydatin comprises a quantity of polydatin, a quantity of lactose, a quantity of starch, a quantity of polyethylene pyrrolidone K30, and a quantity of magnesium stearate. In embodiment 3, 50 g of polydatin, 107 g of lactose, 25 g of starch, 16 g of polyethylene pyrrolidone K30, and 2 g of magnesium stearate are used and that the total weight is 200 g.
The polydatin is mixed with lactose and starch to form a mixture. The mixture is transformed into a granule form by using polyethylene pyrrolidone K30 and passing through a No. 16 model unit. After drying, the granule is mixed with magnesium stearate and pressed into a predetermined shape. Other polydatin in tablet form having different active composition of polydatin can be made by varying the ratio of the quantity of polydatin and vehicle, or the force of pressing device.
A process of making a composition of polydatin in capsule form, comprising the steps of: mixing a quantity of polydatin, a quantity of lactose, a quantity of microcrystalized cellulose, and a quantity of magnesium stearate. In the embodiment 4, 200 capsules having 50 mg active composition of polydatin are prepared from 10 g polydatin, 19.5 g lactose, 10 g microcrystalized cellulose, and 0.5 g magnesium stearate, wherein a total weight is 40 g.
A process of making a composition of polydatin in ointment form, comprising the steps of: mixing and stirring a quantity of polydatin and a quantity of olive oil; and adding a quantity of dissolved white Vaseline while stirring; and mixing thoroughly. The ointment is then canned. In embodiment 5, a 1% polydatin ointment is prepared from 1 g polydatin, 10 g olive oil, and 89 g white Vaseline wherein the total weight is 100 g.
A process of making a composition of polydatin in suppository form, comprising the steps of: mixing and stirring a quantity of polydatin and a quantity of glycerol; and adding a quantity of dissolved glycerol gelatin while stirring; and mixing thoroughly. The suppository is then canned. In embodiment 5, a 1% polydatin suppository is prepared from 1 g polydatin, 5 g glycerol, and 84 g glycerol gelatin wherein the total weight is 100 g.
A treatment action for shock related to blood loss of a composition of polydatin.
The observation is based on the experiment carried out comprising the steps of
(1) anaesthetizing two groups, namely a treatment group and a control group, of SD rats with Urethane Ketamine, inducing bleeding by intubulation at femoral artery and recording blood pressure; wherein femoral vein is used for medication and blood transfusion and cremasteric specimen is prepared by Baez method;
(2) inducing bleeding from femoral artery such that an average arterial blood pressure is maintained between 5.1 to 5.6 kPa;
(3) administering a composition of polydatin injection through femoral vein after one hour wherein the dosage of the composition is 0.6 ml/kg, that the concentration of polydatin is 4 mg/ml and the dosage is 2.4 mg/kg in the treatment group and the composition of polydatin is replaced by physiological saline in the control group;
(4) conducting blood transfusion after 20 minutes such that the volume of blood loss due to bleeding is equal to the volume of blood loss due to blood transfusion; and
(5) observing for two hours and detaching the intubulation.
The records are made by using Olympus microscope, Hitachi monitoring system and physiological recording meter to observe and record microcirculation and blood dynamics. The survival period of each subject of the two groups are recorded.
Result:
(1) Survival period: a ratio of the survival time of the treatment group and the control group is larger than 5.5, wherein 9/10 of the treatment group has a survival period of 24 hours, 8/10 of the treatment group has a survival period of 48 hours, and 6/10 of the treatment group has a survival period of 72 hours. All the subjects in the control group die within 24 hours.
(2) Blood pressure: After experienced shock for 1 hour, the average arterial blood pressure is 5.3+0.2 kPa. After 30 minutes of medication of polydatin, the arterial pressure is increased to 8.6+0.8 kPa in the treatment group, while there is no significant difference in blood pressure in the control group receiving physiological saline.
(3) Diameter of micro blood vessel: After experienced shock for 1 hour, the diameter of micro-aneurysm is reduced to 63.3% of the diameter in average before shock. The diameter is then increased by 20.3% after medication of polydatin and there is no significant difference of diameter in the control group.
(4) Number of opening capillaries: Before shock, the number of open capillary is 5.1±0.4 per μm2. After induced bleeding, the number of open capillary is decreased to 2.2±0.6 per μm2. The number increased to 4.2±0.5 per μm2 in 10 minutes after polydatin medication. There is no significant difference of number of opening capillaries in the control group before and after the administration of physiological saline.
A treatment action for shock related to skin burn of a composition of polydatin.
The observation is based on the experiment carried out comprising the steps of: anaesthetizing two groups, namely a treatment group and a control group, of SD rats with Urethane Ketamine, burning about 35% of body surface below waist for 30 seconds with 80° C. water; administering 0.6 ml/kg polydatin injection (comprising 4 mg/ml polydatin and the dosage is 2.4 mg/kg) by venous injection after half hour of burning in the treatment group and replacing the polydatin injection by physiological saline in control group.
Result: The average survival period of the treatment group is longer than 13.3 hours while the average survival period of the control group is 7.0±2.6 hours.
One skilled in the art will understand that the embodiment of the present invention described above is exemplary only and not intended to be limiting.
It will thus be seen that the objects of the present invention have been fully and effectively accomplished. It embodiments have been shown and described for the purposes of illustrating the functional and structural principles of the present invention and is subject to change without departure form such principles. Therefore, this invention includes all modifications encompassed within the spirit and scope of the following claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 02134928.2 | Oct 2002 | CN | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/CN03/00621 | 8/4/2003 | WO | 00 | 4/4/2005 |
