Use of pharmaceutical compositions in preparing pharmaceuticals for treating diabetic ulcer

Abstract

This invention relates to use of pharmaceutical compositions in preparing pharmaceuticals for treating diabetic ulcer in limb or on body surface, or in preparing medical dressing. The pharmaceutical compositions consist of (A) 3 to 15% by weight of edible beeswax and (B) 85 to 97% by weight of sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, based on the total weight of the pharmaceutical compositions. In the sesame oil extract, each of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is in an amount of 2 to 10% by weight of dry raw material based on the total weight of sesame oil. This invention also relates to a medical dressing for treating diabetic ulcer and corresponding medicine box enclosing the said dressing.

Claims

1. A method for treating diabetic foot gangrene comprising administering to a patient in need thereof an effective amount of one pharmaceutical composition consisting of (A) 3 to 15% by weight of edible beeswax and (B) 85 to 97% by weight of sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, based on the total weight of the pharmaceutical compositions, while in the sesame oil extract, each of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is in an amount of 2 to 10% by weight based on the total weight of sesame oil.

2. The method according to claim 1, characterized in that said composition is externally applied.

3. The method according to claim 2, characterized in that said externally applied composition is in the form of an oil, emulsion, paste, emplastrum or gel.

4. A method for treating diabetic foot gangrene comprising administering to a patient in need thereof an effective amount of one pharmaceutical composition consisting of (a) 3 to 15% by weight of edible beeswax; (b) 85 to 97% by weight of sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, based on the total weight of the pharmaceutical compositions, while in the sesame oil extract, each of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is in an amount of 2 to 10% by weight based on the total weight of sesame oil and (c) at least one pharmaceutically acceptable carrier.

5. A method for treating diabetic foot gangrene comprising administering to a patient in need thereof an effective amount of one pharmaceutical composition, wherein the pharmaceutical composition is in a medical dressing, wherein the pharmaceutical composition consist of: (A) 3 to 15% of edible beeswax and (B) 85 to 97% of sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, based on the total weight of the pharmaceutical composition, and, optionally, (C) at least one pharmaceutically acceptable carrier, wherein in the sesame oil extract, each of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is in an amount of 2 to 10% by weight based on the total weight of sesame oil.

6. The method according to claim 5, characterized in that said medical dressing comprises medical cotton gauze and medical bandage.

7. The method according to claim 6, characterized in that said pharmaceutical composition is in the form of an oil, emulsion, paste, emplastrum or gel.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

(1) FIG. 1: Picture of diabetic ulcer in left external malleolus of the diabetic patient described in Example 7.

(2) FIG. 2: Picture of pasting and smearing medical gauze on the ulcer of the diabetic patient described in Example 7.

(3) FIG. 3: Picture of treatment progress of the ulcer in left external malleolus of the diabetic patient described in Example 7.

(4) FIG. 4: Picture of treatment progress of the ulcer in left external malleolus of the diabetic patient described in Example 7.

(5) FIG. 5: Picture of treatment progress of the ulcer in left external malleolus of the diabetic patient described in Example 7.

(6) FIG. 6: Picture of the ulcer in left external malleolus of the diabetic patient described in Example 8.

(7) FIG. 7: Picture of pasting and smearing medical gauze on the ulcer for the diabetic patient described in Example 8.

(8) FIG. 8: Picture of pasting and smearing on the ulcer for the diabetic patient described in Example 8.

(9) FIG. 9: Picture of diabetic ulcer before treatment of the diabetic patient described in Example 9.

(10) FIG. 10: Picture of diabetic ulcer amid treatment of the diabetic patient described in Example 9.

(11) FIG. 11: Picture of diabetic ulcer after treatment of the diabetic patient described in Example 9.

(12) FIG. 12: Picture of diabetic ulcer before treatment of the diabetic patient described in Example 10.

(13) FIG. 13: Picture of diabetic ulcer after treatment of the diabetic patient described in Example 10.

(14) FIG. 14: Picture of diabetic ulcer after treatment of the diabetic patient described in Example 10.

(15) FIG. 15: Picture of diabetic ulcer after treatment of the diabetic patient described in Example 10.

(16) FIG. 16: Picture of treatment with emplastrum for the diabetic patient described in Example 11 of Implementation.

(17) FIG. 17: Picture of day 31 post treatment for the diabetic patient described in Example 11.

(18) FIG. 18: Picture of day 60 post treatment for the diabetic patient described in Example 11.

(19) FIG. 19: Picture of day 90 post treatment for the diabetic patient described in Example 11.

(20) FIG. 20: Picture of day 110 post treatment for the diabetic patient described in Example 11.

EXAMPLES

(21) Next, with the aid of attached pictures, the present invention will be explained further by way of the following non-limited examples. Persons skilled in the art all know and agree that, without departing from the spirit of this present invention, many modifications can be made to the present invention, but, even so, all the said modifications will also fall into the category of this present invention. In addition, all raw material including Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, sesame oil can be easily obtained in the market.

Example 1

(22) In accordance with the method revealed in Example 1 in Chinese Patent ZL931002761, and according to the detailed and the same raw material revealed, sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule is obtained. By mixing the above-mentioned sesame oil extract and beeswax, Pharmaceutical Composition 1 described in the present invention is obtained.

Example 2

(23) According to the same method described in Chinese Patent ZL931002761, the pharmaceutical composition described in the present invention is manufactured, except that 10 Kg of each of Huanglian, Huangqin and Huangbai pieces, 2 kg of each of earthworm and poppy capsule, 100 Kg of sesame oil and 10 Kg of beeswax are used. By mixing the beeswax and sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, Pharmaceutical Composition 2 is obtained.

Example 3

(24) According to the same method described in Example 1 of the present invention, the pharmaceutical composition described in the present invention is manufactured, except that 8 Kg of each of Huanglian, Huangqin and Huangbai pieces, 3 kg of each of earthworm and poppy capsule, 100 Kg of sesame oil and 8 Kg of beeswax are used. By mixing the beeswax and sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, Pharmaceutical Composition 3 is obtained.

Example 4

(25) According to the same method described in Chinese Patent ZL931002761, the pharmaceutical composition described in the present invention is manufactured, except that 3 Kg of each of Huanglian, Huangqin and Huangbai pieces (prepared pieces in the art,), 4 kg of each of earthworm and poppy capsule, 100 Kg of sesame oil and 15 Kg of beeswax are used. By mixing the beeswax and sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, Pharmaceutical Composition 4 is obtained.

Example 5

(26) According to the same method described in Example 3 of the present invention, the pharmaceutical composition described in the present invention is manufactured, except that 10 Kg of each of Huanglian, Huangqin and Huangbai pieces, 10 kg of each of earthworm and poppy capsule, 100 Kg of sesame oil and 3 Kg of beeswax are used. By mixing the beeswax and sesame oil extract of Huangqin, Huanglian, Huangbai, earthworm and poppy capsule, Pharmaceutical Composition 5 is obtained.

Example 6

(27) The pharmaceutical compositions in the present invention obtained in Example 1 to 5 of are warmed up and melted. According to the method known to the persons skilled in the art, the medical gauze is immersed directly into each of the five pharmaceutical compositions respectively until it is completely soaked, thus medical dressing containing the pharmaceutical compositions of this present invention is obtained. The dressing was packed into marketable medical products.

Example 7

(28) Treatment for the ulcer of the malleolus soft tissue in diabetic patient

(29) Diabetic patient, male, 59 years old, left external malleolus ulcerated for 2 years, with an area of about 4×4 cm (see FIG. 1), diagnosed in confirmation as diabetic ulcer. After admission, expectant treatment of lowering blood sugar was adopted, and the medical gauze described in Example 6 prepared from pharmaceutical composition manufactured according to method described in Example 1 was used. The ulcerous wound surface was pasted and covered with the dressing (see FIG. 2 and FIG. 3), which was changed once daily. The patient was healed and discharged after treatment for one month (see FIG. 4 and FIG. 5).

Example 8

(30) Treatment for the ulcer of the malleolus soft tissue in diabetic patient

(31) Diabetic patient, male, 58 years old, left internal malleolus ulcerated for 2 years, with an area of about 3.5×4 cm (see FIG. 6), diagnosed in confirmation as diabetic ulcer. After admission, expectant treatment of lowering blood sugar was adopted, and the medical gauze described in Example 6 made from pharmaceutical composition manufactured according to method described in Example 2 used. The ulcerous wound surface was pasted and covered with the dressing (see FIG. 7), which was changed once daily. The patient was healed and discharged after treatment for one month (see FIG. 8).

Example 9

(32) Treatment for Diabetic Foot Ulcer

(33) Diabetic patient, female, 42 years old, came to see the doctor after left foot ulcerated for 22 days and began to exacerbate. Amputation had been advised by doctors but was rejected by her. On admission, fasting blood sugar in early morning was 22.67 mmol/L, and the patient was clinically diagnosed in confirmation as diabetes. Serious diabetic ulcer appeared in the internal and lower site of the left foot, with remarkable swelling of left foot, intensive ulceration from external portion of foot dorsum to middle and rear portion of planta, meanwhile fistulous tracts formed and linked up, phalanges of toes exposed, fasciae and muscles began to necrotize, ulcerate and was fetid (see FIG. 9). After anti-infection and nutritional support therapy, the patient was smeared with the pharmaceutical composition described in Example 3 with a thickness of about 2 mm on the ulcer, subsequently the ulcerous wound surface which was covered with the pharmaceutical composition was completely exposed. The pharmaceutical was changed once daily (see FIG. 10). After treatment for 45 days, the ulcer basically healed and the patient was discharged from the hospital (see FIG. 11).

Example 10

(34) Treatment for Diabetic Foot Ulcer

(35) Male, suffered from diabetes for many years, blood sugar was not controlled very well in everyday life, a diabetic ulcer in left malleolus was clinically diagnosed, internal portion of distal end of left foot was obviously red and swelling, there were open wounds in hallux and phalangeal joint, joint capsule was damaged, bone articular surface could be seen, there was necrotic tissue attached to internal portion of bone's distal end, muscle tendon swelled and denatured. There was a wound surface of 8×6 cm in planta, fetid and with secretion (see FIG. 12). The patient was smeared with the pharmaceutical composition described in Example 4 with a thickness of about 1.5 mm on the ulcer, subsequently the ulcerous wound surface which was covered with the pharmaceutical composition was completely exposed. The pharmaceutical was changed once daily. After treatment for 35 days, the said ulcer healed and the patient was discharged from the hospital (see FIG. 13, FIG. 14, FIG. 15).

Example 11

(36) Treatment for Diabetic Foot Ulcer

(37) Xu, male, 59 years old, suffered from diabetes for 20 years. He went to see doctor in a Chinese provincial hospital because of his diabetic foot gangrene. The doctor advised him to be amputated, but he did not agree and then was transferred to The First Clinical Hospital affiliated to Harbin Medical University. Diagnosis on admission showed: (1) Type I diabetes; (2) diabetic gangrene of right foot due to arterial obliteration in right leg for half a year. After management to ulcerous wound surface, the patient was treated with ointment form of the pharmaceutical composition described in Example 2, and emplastrum form (containing pharmaceutical composition described in Example 3) described in Example 6 (see FIG. 16). The pharmaceutical was changed once daily and the ulcer was treated with ointment and emplastrum alternatively after exposure. Ulcerous wound surface healed gradually [see FIG. 17 (day 31), FIG. 18 (day 60)], on day 90, ulcerous wound surface basically healed (see FIG. 19). After treatment for 110 days, ulcerous wound surface healed well (see FIG. 20).

Example 12

(38) Observation of Therapeutic Effectiveness on Diabetic Ulcers of the Lower Extremities in 60 Cases

(39) In 60 cases of diabetic ulcer on leg, 36 cases were for male and 24 for female. Aged from 60 to 80 years old, all patients had symptoms of polyposia, diuresis, polyphagia, hypodynamia and so on. Tests repeatedly showed that level of fasting blood sugar was higher than 7.8 mmol/L, which was in accordance with the diagnosis of type II diabetes. Among all the cases in which the ulcers of the lower extremities lasted from 1 month to 26 months, 15 were acute ulcer, 45 were chronic ulcer. Among all the latter that had accepted treatment in other hospitals, there were 36 cases of toe ulcer, 9 cases for each of heel ulcer and metatarsus ulcer, and 6 cases of pretibial ulcer. All the foot ulcers were chronic and deep down to fatty layer and ulcerous wound surfaces lacked granulation tissue, dry and little exudative. The minimum area was 2.0 cm×1.0 cm and the maximum area was 2.2 cm×5.5 cm. Foot ulcers were surrounded by thick and hard callous tissue. 5 in 6 cases of pretibial ulcer were caused by external wounds, all with area less than 2.0 cm×3.5 cm, obvious red, swelling, itching and pain of the surrounding skin. All the cases were divided into two groups by randomization: 30 cases for observation group and 30 cases for control group. There was no significant difference (P>0.05) in statistics between the two groups in age, sex, disease phase, and the ulcerous size. As to treatment for primary diseases, besides intensifying dietotherapy, reducing blood sugar level with corresponding drugs was applied for all cases. To avoid hypoglycemia and lactacidemia in elderly patients, Acarbose was given. The blood sugar concentration was regularly tested and the therapeutic plans were readjusted accordingly. The most ideal treatment effect for primary diseases is that the blood sugar concentration is lower than 8.3 mmol/L.

(40) In observation group (test group), the ulcerous wound surface and the surrounding skin was disinfected with 1% povidone-iodine, cleaned with sterile normal salt solution, and the necrotic tissue was cleared with sterile forceps and scissors, then cleaned with sterile normal salt solution or 3% hydrogen peroxide solution. All the ulcers in observation group were externally and topically applied povidone-iodine evenly allowing the drug to infiltrate into the tissue for 1 to 2 minutes. Then the pharmaceutical composition of the present invention described in Example 1 was smeared on the ulcers with cotton swabs, wiped flat, maintained a thickness of 1.5 mm to 2.0 mm. Sterile gauze was placed on the ointment, bandaged. With the sick legs raised, the pharmaceutical was changed once daily. The therapeutic strategy was changed to moisturizing exposed method when the necrotic tissue began to liquefy. With a thickness of 1.0 mm, the pharmaceutical was changed twice daily. The liquefied necrotic tissue was cleared in time when changing the pharmaceutical each time.

(41) In control group, the sterile gauze was soaked in 160,000 U of Gentamycin, and then applied to the ulcers bandaged with dressing once daily. When changing, liquefied mixture or the necrotic tissue in the ulcers in two groups should be cleared away, until the granulation tissue grew and epithelization completely realized.

(42) Using graph-drawing method and transparent graph paper to determine the healing rate of ulcerous wound surface, to calculate the area of ulcerous wound surface, refer to Adobe Photoshop 7.0 and Osiris softwares for details. The area before treatment was selected as the initial area, and the area at the end of the research as time phase point area. Formula for calculating area: healed area=(initial area)−(time phase point area); healing rate of ulcerous wound surface=(healed area/lesion area)×100%. Healing+obvious effectiveness+effectiveness=total effectiveness. Healing: complete epithelization, no exudate; Obvious effectiveness: healing rate is over 80%, no secretion, granulation tissue grow obviously, fresh and liable to bleeding; Effectiveness: ulcerous wound surfaces shrink, but not up to 80%, exudate diminishes, granulation tissue proliferates, pale or not fresh; Ineffectiveness: ulcerous wound surfaces do not change or even expand, not fresh.

(43) Through statistical processing, all data were expressed as (x±S). Statistical analysis including r test, X.sup.2 test, and correlation analysis for enumeration data were undertaken with SPSS11.0 statistics software. P<0.05 represents statistical significance.

(44) In the above-mentioned cases, 6 cases of pretibial ulcers healed within 4 weeks, and the healing course was similar to that of burns of deep second degree. The healed topical skin is flat. The shortest healing time of chronic ulcers in toes and heels was 35 days and the longest was 2 months. According to clinical observation, the whole healing course of this type of ulcer can be divided into three stages: Liquefaction and excretion of necrotic tissue; formation of transparent lipoprotein membrane; and regenerative healing. Time span for liquefaction and excretion of necrotic tissue is related to the types of primary diseases and necrotic intensification of ulcerous wound surface, but all necrotic tissue can begin to liquefy after treatment for 3 to 4 days, and liquefaction and excretion will finish within 2 to 4 weeks. The second and the first stages are linked up, i.e., transparent lipoprotein membrane develops step by step during the liquefaction and excretion of necrotic tissue, and liquefaction and excretion of necrotic tissue finishes when transparent lipoprotein membrane completely forms. Once that transparent lipoprotein membrane forms, regenerative repair will accelerate, macroscopically, patch-like skin nails or skin islands grows and expands. Along with the treatment, callous tissue surrounding wound surface will gradually exfoliate, newly grown skin will emerge and grow concentrically, and finally ulcerous wound surfaces repair themselves.

(45) TABLE-US-00001 TABLE Comparison of therapeutic effectiveness between two groups. Mean Case Obvious Effective- Ineffective- Total heading Group No. Healing effectiveness ness ness effectiveness time (d) Control 30  9 12 6 3 27 47.30 ± 20.40 group Test 30 27  2 1 0 30 25.00 ± 10.05 group Note: X.sup.2test for the data of row × column table was adopted for comparison of rate, X.sup.2 values of effectiveness rate and healing rate are 22.71 and 20.07 respectively, all are more than X.sub.0.05.sup.2 = 12.84, therefore P < 0.05; X.sup.2 test was also adopted for comparison of mean healing times, t = 5.32, P < 0.01.

Example 13

(46) A kind of medicine box was manufactured using pharmaceutical composition obtained from Example 1, or medical dressing obtained from Example 6 with a method known in the art. Finally, the printed Directions for Use were combined with the respectively packed pharmaceutical compositions (e.g., ointment) or the said medical dressing (e.g., emplastrum) and became marketable medicine box after packing.