CA2095439C - Substance that stops any bleeding on contact for medical, surgical and dental uses - Google Patents
Substance that stops any bleeding on contact for medical, surgical and dental usesInfo
- Publication number
- CA2095439C CA2095439C CA 2095439 CA2095439A CA2095439C CA 2095439 C CA2095439 C CA 2095439C CA 2095439 CA2095439 CA 2095439 CA 2095439 A CA2095439 A CA 2095439A CA 2095439 C CA2095439 C CA 2095439C
- Authority
- CA
- Canada
- Prior art keywords
- bleeding
- blood
- coagulation
- powder
- contact
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000000740 bleeding effect Effects 0.000 title abstract description 54
- 239000000126 substance Substances 0.000 title 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 78
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 18
- 229930003268 Vitamin C Natural products 0.000 claims description 18
- 235000019154 vitamin C Nutrition 0.000 claims description 18
- 239000011718 vitamin C Substances 0.000 claims description 18
- 229960005070 ascorbic acid Drugs 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000011668 ascorbic acid Substances 0.000 claims description 10
- 235000010323 ascorbic acid Nutrition 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000000701 coagulant Substances 0.000 claims 1
- 235000010378 sodium ascorbate Nutrition 0.000 claims 1
- 229960005055 sodium ascorbate Drugs 0.000 claims 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
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- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- 108010054218 Factor VIII Proteins 0.000 description 2
- 102000001690 Factor VIII Human genes 0.000 description 2
- 206010016717 Fistula Diseases 0.000 description 2
- 235000000069 L-ascorbic acid Nutrition 0.000 description 2
- 239000002211 L-ascorbic acid Substances 0.000 description 2
- 206010062575 Muscle contracture Diseases 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 208000006111 contracture Diseases 0.000 description 2
- 230000003890 fistula Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 201000003542 Factor VIII deficiency Diseases 0.000 description 1
- 206010017826 Gastric ulcer haemorrhage Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229940089602 epinephrine injection Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000004023 fresh frozen plasma Substances 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 229940090044 injection Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- -1 material is formed Chemical compound 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000005900 regulation of collagen biosynthetic process Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Dental Preparations (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
There is disclosed a method for stopping bleeding and forming black blood coagulation on contact, comprising administering powdered L-threo-hex-2-enono-1,4-lactone thereof to a wound site in an amount of 0.1568 grams for every milliliter of blood. This includes cancer, liver disease and hemophiliac bleeding in patients or animals in whom the thrombocytopenia or coagulation factor disorders result. Accordingly, the said mechanism of action of powdered L-threo-hex-2-enono-1,4-lactone in the formation of blood coagulation on contact is the unique common pathway for all blood coagulations, which overturns the mechanisms of intrinsic and extrinsic pathways for blood coagulation cascade being the unique pathways for blood coagulation in which the coagulation factors 1, 2, 5, 7, 8, 9, 10 and platelet factor 3 are essential for the pathways.
Description
Patent Application No: 2,095,439 SUBSTITUTE SPECIFICATION
CROSS REFERENCE RELATED TO APPLICATION
This application is an international application for U.S.
application Serial No. 07/624,09~, filed 06 Decemher, 1990.
BACKGROUND OF THE INVENTION
The present invention pertains to the field of blood coagula- -tion, which is further related to evaluation of coagulation tests ; e. g. prothrombin time, partial thromboplastin time and activa-ted partial thromboplastin time etc, and coagulation factor dis-orders. However, the blood coagulation mechanism of action of po-wdered L-Ascorbic acid which was administered topically does not fall into either intrinsic or extrinsic pathway cascade of blood coagulation scheme, since it works the same for blood coagulation in normal situation as in chronic hepatitis, colon cancer, and he-mophilia patients in whom the coagulation factors 1, 2, 5, 7, 9, and 10 and platelets in the liver disease and factor 8 or 9 in the hemophilia A or B are abnormal, or suppressed the syntheses, and destroyed and deficient ( Harrison's Principles of Internal Medicine, 12th Edition, l991, Pages 181~-1315 ). In other words, powdered L-Ascorbic acid or L-threo-hex-2-enono-1,4-lactone stops any bleeding and forms hlack blood coagulation on contact, with the same amount of powdered ~-Ascorbic acid per unit volume of bl-ood for any normal or diseased blood.
The present methods available to stop bleeding in surgery are cautery, epinephrine injection, pressure and some fiber foam. The cautery can cause tissue necrosis in some cases. The epinephrine, pressure and fiber foam can not work for bleeding tendency pati-ents, and fiber foam can cause tissue hematoma, nor can they work for diffuse capillary bleeding and oozing, while powdered ascor-bic acid does not cause any tissue necrosis and work particularly well for diffuse capillary bleeding and oozing and any tradition-ary uncontrollable bleeding tendency patients such as for patients with liver diseases, hemophilia and rectal anal cancer and for po-stoperation bleeding tendency of the kinds of aforementioned pa-tients. The ascorbic acid can facilitate wound healing also ( Ora-1 Surg 1982 Mar: 53(3): 231-6 ) ky increasing type 1 procollagen CA 0209~439 1998-04-29 _~nRNA in the regulation of collagen synthesis ( Atherosclerosis 1982 Jan: 41(1): 15-9 ).
SUMMARY OF THE INVENTION
The present invention is directed to a method for stopping blee-ding, comprising administering powdered vitamin C thereof to the wound site caused by pathological changes, trauma or surgery, in an amount of 0.1568 grams for every milliliter of blood. Powdered 1-threo-hex-2-enono-1,4-lactone represents ascorbic acid powder.
This powder has a very potent coagulation action to stop bleeding when spraying topically on the bleeding area for any normal or diseased patients. When the powder comes in contact with the blood, the black tar like material is formed, and later becomes solid.
The amount of the powder that is needed to react completely with the blood is proportional to the amount of the blood that comes out of the blood vessels. In rats, one capillary, one venous and one femoral artery bleeding were stanched within one second, if sufficient amount of the powder of ascorbic acid were applied.
The artery bleeding needs much more this powder of interest. In the test tube conditions, it requires 0.1568 grams of powdered ~-Ascorbic acid or L-threo-hex-2-enono-1,4-lactone added to 1 ml of any normal or diseased human blood to turn the mixture black and, after 6 minutes, it does not move by shaking or pouring; this is the same for normal, colon cancer and hemophilia patients; 1 ml of normal blood needs 0,1568 grams of ascorbic acid powder, 1 ml of colon cancer needs 0.1568 grams of ascorbic acid powder, and 1 ml of hemophilia blood needs 0.1568 grams of ascorbic acid powder.
Sufficient powdered L-threo-hex-2-enono-1,4-lactone is particula-rly useful to stop bleeding in the case of diffuse capillary oo-zing and mistakenly cut off artery or arteries that can not be found during massive bleeding so as to save the patients's lives therefor. When vitamin C is absorbed into the system, it is good for health by making the leucocytes stronger and slowing the aging process etc, ( Patnaik and Kanungo 1964, Gerontologia, 10, 155 ).
However, at the end of operation before closure, the excessive black tar gel like material can be wiped away with Ringer's solu-tion.
DETAILED DESCRIPTION OF THE INVENTION
I CA 0209~439 1998-04-29 "l",,,~
The present invention is grounded on applicant's discovery that any bleeding, either normal or diseased blood, is stopped on con-tact, and is formed black blood coagulation, by administration to-pically of a composition comprising powdered vitamin C to the ble-eding sites even when contaminated with impurities, and excipients, in an amount of 0.1568 grams of powdered vitamin C for every mil-liliter of blood. A composition comprising powdered vitamin C is made by making vitamin C tablets into powder. A vitamin C tablets, of course, contains impurities, and excipients other than vitamin C. While the present method is particularly directed at treatment of bleeding in humans it finds the same application for veterinary use. As the liver is the site of syntheses of all coagulation fac-tors except 8, prior to the present invention, nothing has, to the best of my knowledge, been made to stop bleeding on contact, for the massive bleeding tendency patients afflicated with liver dise-ases, cancer or hemophilia. The treatment for hepatic coagulopathy and hemophilia is the replacement therapy for transfusion of fresh frozen plasma and factor 8 or 9 concentrates respectively, Lawrence M. Tierney, Jr., et al, Current Medical Diagnosis & Treatment, 199~ rd Annual Revision, A58-~59, but that will not bleeding on time in a wound caused by trauma or surgery; some patients bled to death simply because of e~traction of teeth or tonsilectomy. As so-on as a composition comprising powdered vitamin C contacts with bl-ood, even in massive bleeding when an artery of a rat is cut off, the blach gel film like structure forms on the surface of the pond of blood, that stops the fluid of blood moving. If stirring the bl-ood to break through the surface film like structure that keeps fl-uid from moving when the powder is insufficient, it will bleed aga-in, but much slower than before pouring into the bleeding area;
adding sufficient powder into the blood, stirring makes the powder molecules well saturated with the hemoglobin and plasma protein mo-cules and thus forming the concentrated black sticky gel like stru-cture.
The invention is further illustrated in the following examples, none of which are to be construed as limiting the invention in any respect. The following example reports the results of an animal study and a clinical evidence of a composition or the present inve-ntion in the treatment of bleeding.
CA 0209~439 1998-04-29 Sufficient composition comprising powdered vitamin C stops massive bleeding of femoral artery on contact when femoral artery of a rat is cut off. In this case of artery bleeding, it is administered topically by pouring instead of spraying. Although the amount of the powder needed varies with rats, 0.1344 grams is usually suff-icient to stop bleeding within one second for the femoral artery of a rat. The black tar like material is formed in one second as soon as the powder contacts with the blood. When sufficient amount of powdered vitamin C is present, stirring make more blood molecu-les interact with ascorbic acid molecules so as to form more con-centrated and sticky black gel like coagulation. After 5-6 minutes, when most of the sticky tar like structure is wiped away, it appe-ars there is no bleeding at all.
In the case of capillary bleeding in which one capillary is cut off, about 0.0112 grams of this powder stops the bleeding on contact.
After 1 minute count from adding the powder, it appears there is no more bleeding at all in a rat.
While in the case of one vein cut off in a rat, it needs about 0.
0224 grams of the powder to stop bleeding on contact, ~bout 1 1/2 minutes after the black coagulation is wiped away, it appears the-re is no more bleeding.
The nostril of a rat is cut slightly to bleed, the bleeding stops on contact when applying 0.00~7 grams of this powder to the blee-ding nostril.
After injection of histamin into the rat, it induces secretion of gastric acid, applying the powder topically to the bleeding area, the black coagulation formed, but slower than normal, since the secretion dilutes the black coagulation. Thus this powder can tre-at the gastric ulcer bleeding when ingested orally.
CLINICAL EVIDENCE EX~MPLE 6 ~' CA 0209~439 1998-04-29 4 Scalp Tumor Excision Age 32, male, scalp tumor excision, massive bleeding when the tu-mor is excised. Sufficient spraying this powder to the bleeding area, the bleeding stops on contact, after the coagulation is wa-shed away, it is closed by suture.
A-V Fistula Plasty Ase 40, female, acute renal failure, A-V fistula formation opera-tion, massive bleeding. The operation of stopping bleeding consi-sts of combing the powder with pressing with gauzes. When admini-stering this powder to the bleeding area, those that look black in color indicate the black coagulation, while those that are white are the powder that does not get mixed up with the blood yet. At the end of the operation, most of black blood coagulation is wi-ped out with 4x4 gauze, and rinsed with Ringer's solution. It tak-es totally 5 minutes to stop bleeding completely, as the surgeon kept wiping away the coagulation. The patient's conditions are particularly well, better than without using this powder.
Skin Contracture Excision Age 40, male, skin contracture on the palm, which needs to be re-moved, and it requires skin graft. When the skin graft is removed from the hand, massive bleeding occurs. On applying sufficient pow-der to the bleeding area topically, it appears black coagulation on contact. Bleeding stops at the same time as the black coagula-tion forms. Those that appears white indicate the powder not yet get mixed up with the blood. Those that appears more black area indicate the more powder mixed up with the blood. Suture going on.
Paraanal Abscess Excision Age 70, female, paraanal excision, bleeding when it is opened up.
When spraying the powder to the bleeding area, it stops bleeding by forming black blood coagulation on contact. Those that appears white are the powder that are not mixed up with the blood. Suture going on.
[ CA 0209~439 1998-04-29 .
Paraanal Abscess Excision Age 50, male, paraanal abscess excision, massive bleeding when it is opened. On spraying the powder topically to the bleeding area, the black color is formed on contact because of the blood coagula-tion. The white color is the powder instantly not mixed up with the blood yet. Lastly, insert the long gauze into the anus.
Extraction of Teeth Age 30, male, extraction of teeth, gum injected bleeds. Administ-ering this powder topically to the bleeding area, the bleeding sto-ps on contact and black blood coagulation forms at the same time.
Wipe out the black coagulation in 10 seconds, stopped bleeding still persisted.
Extraction of Teeth for Chronic Hepatitis Age 60, female, chronic hepatitis, has bleeding tendency, extrac-tion of teeth causes massive bleeding. Upon applying this powder to the socket of the gum, the black coagulation forms on contact, and the bleeding in the socket stops on contact accordingly.
Finger Scratched Myself, finger little scratched, slightly bleeds. Upon contact with the powder, the black color forms on contact.
Normal, Liver Disease, Colon Cancer and Hemophilia Blood When tested in the tube, 1 milliliter of human blood requires 0.15 68 grams of powdered vitamin C to form black blood coagulation by shaking the tube with hand or stirrer machine. It takes 6 minutes to cause the black blood coagulation unmobile in the test tube for normal, liver diseases, colon cancer and hemophilia blood respec-tively. These experiments have evidenced that the mechanism of action of powdered vitamin C in the formation of black blood coa-gulation does not involve the coagulation factors.
~F
~ CA 0209~439 1998-04-29
CROSS REFERENCE RELATED TO APPLICATION
This application is an international application for U.S.
application Serial No. 07/624,09~, filed 06 Decemher, 1990.
BACKGROUND OF THE INVENTION
The present invention pertains to the field of blood coagula- -tion, which is further related to evaluation of coagulation tests ; e. g. prothrombin time, partial thromboplastin time and activa-ted partial thromboplastin time etc, and coagulation factor dis-orders. However, the blood coagulation mechanism of action of po-wdered L-Ascorbic acid which was administered topically does not fall into either intrinsic or extrinsic pathway cascade of blood coagulation scheme, since it works the same for blood coagulation in normal situation as in chronic hepatitis, colon cancer, and he-mophilia patients in whom the coagulation factors 1, 2, 5, 7, 9, and 10 and platelets in the liver disease and factor 8 or 9 in the hemophilia A or B are abnormal, or suppressed the syntheses, and destroyed and deficient ( Harrison's Principles of Internal Medicine, 12th Edition, l991, Pages 181~-1315 ). In other words, powdered L-Ascorbic acid or L-threo-hex-2-enono-1,4-lactone stops any bleeding and forms hlack blood coagulation on contact, with the same amount of powdered ~-Ascorbic acid per unit volume of bl-ood for any normal or diseased blood.
The present methods available to stop bleeding in surgery are cautery, epinephrine injection, pressure and some fiber foam. The cautery can cause tissue necrosis in some cases. The epinephrine, pressure and fiber foam can not work for bleeding tendency pati-ents, and fiber foam can cause tissue hematoma, nor can they work for diffuse capillary bleeding and oozing, while powdered ascor-bic acid does not cause any tissue necrosis and work particularly well for diffuse capillary bleeding and oozing and any tradition-ary uncontrollable bleeding tendency patients such as for patients with liver diseases, hemophilia and rectal anal cancer and for po-stoperation bleeding tendency of the kinds of aforementioned pa-tients. The ascorbic acid can facilitate wound healing also ( Ora-1 Surg 1982 Mar: 53(3): 231-6 ) ky increasing type 1 procollagen CA 0209~439 1998-04-29 _~nRNA in the regulation of collagen synthesis ( Atherosclerosis 1982 Jan: 41(1): 15-9 ).
SUMMARY OF THE INVENTION
The present invention is directed to a method for stopping blee-ding, comprising administering powdered vitamin C thereof to the wound site caused by pathological changes, trauma or surgery, in an amount of 0.1568 grams for every milliliter of blood. Powdered 1-threo-hex-2-enono-1,4-lactone represents ascorbic acid powder.
This powder has a very potent coagulation action to stop bleeding when spraying topically on the bleeding area for any normal or diseased patients. When the powder comes in contact with the blood, the black tar like material is formed, and later becomes solid.
The amount of the powder that is needed to react completely with the blood is proportional to the amount of the blood that comes out of the blood vessels. In rats, one capillary, one venous and one femoral artery bleeding were stanched within one second, if sufficient amount of the powder of ascorbic acid were applied.
The artery bleeding needs much more this powder of interest. In the test tube conditions, it requires 0.1568 grams of powdered ~-Ascorbic acid or L-threo-hex-2-enono-1,4-lactone added to 1 ml of any normal or diseased human blood to turn the mixture black and, after 6 minutes, it does not move by shaking or pouring; this is the same for normal, colon cancer and hemophilia patients; 1 ml of normal blood needs 0,1568 grams of ascorbic acid powder, 1 ml of colon cancer needs 0.1568 grams of ascorbic acid powder, and 1 ml of hemophilia blood needs 0.1568 grams of ascorbic acid powder.
Sufficient powdered L-threo-hex-2-enono-1,4-lactone is particula-rly useful to stop bleeding in the case of diffuse capillary oo-zing and mistakenly cut off artery or arteries that can not be found during massive bleeding so as to save the patients's lives therefor. When vitamin C is absorbed into the system, it is good for health by making the leucocytes stronger and slowing the aging process etc, ( Patnaik and Kanungo 1964, Gerontologia, 10, 155 ).
However, at the end of operation before closure, the excessive black tar gel like material can be wiped away with Ringer's solu-tion.
DETAILED DESCRIPTION OF THE INVENTION
I CA 0209~439 1998-04-29 "l",,,~
The present invention is grounded on applicant's discovery that any bleeding, either normal or diseased blood, is stopped on con-tact, and is formed black blood coagulation, by administration to-pically of a composition comprising powdered vitamin C to the ble-eding sites even when contaminated with impurities, and excipients, in an amount of 0.1568 grams of powdered vitamin C for every mil-liliter of blood. A composition comprising powdered vitamin C is made by making vitamin C tablets into powder. A vitamin C tablets, of course, contains impurities, and excipients other than vitamin C. While the present method is particularly directed at treatment of bleeding in humans it finds the same application for veterinary use. As the liver is the site of syntheses of all coagulation fac-tors except 8, prior to the present invention, nothing has, to the best of my knowledge, been made to stop bleeding on contact, for the massive bleeding tendency patients afflicated with liver dise-ases, cancer or hemophilia. The treatment for hepatic coagulopathy and hemophilia is the replacement therapy for transfusion of fresh frozen plasma and factor 8 or 9 concentrates respectively, Lawrence M. Tierney, Jr., et al, Current Medical Diagnosis & Treatment, 199~ rd Annual Revision, A58-~59, but that will not bleeding on time in a wound caused by trauma or surgery; some patients bled to death simply because of e~traction of teeth or tonsilectomy. As so-on as a composition comprising powdered vitamin C contacts with bl-ood, even in massive bleeding when an artery of a rat is cut off, the blach gel film like structure forms on the surface of the pond of blood, that stops the fluid of blood moving. If stirring the bl-ood to break through the surface film like structure that keeps fl-uid from moving when the powder is insufficient, it will bleed aga-in, but much slower than before pouring into the bleeding area;
adding sufficient powder into the blood, stirring makes the powder molecules well saturated with the hemoglobin and plasma protein mo-cules and thus forming the concentrated black sticky gel like stru-cture.
The invention is further illustrated in the following examples, none of which are to be construed as limiting the invention in any respect. The following example reports the results of an animal study and a clinical evidence of a composition or the present inve-ntion in the treatment of bleeding.
CA 0209~439 1998-04-29 Sufficient composition comprising powdered vitamin C stops massive bleeding of femoral artery on contact when femoral artery of a rat is cut off. In this case of artery bleeding, it is administered topically by pouring instead of spraying. Although the amount of the powder needed varies with rats, 0.1344 grams is usually suff-icient to stop bleeding within one second for the femoral artery of a rat. The black tar like material is formed in one second as soon as the powder contacts with the blood. When sufficient amount of powdered vitamin C is present, stirring make more blood molecu-les interact with ascorbic acid molecules so as to form more con-centrated and sticky black gel like coagulation. After 5-6 minutes, when most of the sticky tar like structure is wiped away, it appe-ars there is no bleeding at all.
In the case of capillary bleeding in which one capillary is cut off, about 0.0112 grams of this powder stops the bleeding on contact.
After 1 minute count from adding the powder, it appears there is no more bleeding at all in a rat.
While in the case of one vein cut off in a rat, it needs about 0.
0224 grams of the powder to stop bleeding on contact, ~bout 1 1/2 minutes after the black coagulation is wiped away, it appears the-re is no more bleeding.
The nostril of a rat is cut slightly to bleed, the bleeding stops on contact when applying 0.00~7 grams of this powder to the blee-ding nostril.
After injection of histamin into the rat, it induces secretion of gastric acid, applying the powder topically to the bleeding area, the black coagulation formed, but slower than normal, since the secretion dilutes the black coagulation. Thus this powder can tre-at the gastric ulcer bleeding when ingested orally.
CLINICAL EVIDENCE EX~MPLE 6 ~' CA 0209~439 1998-04-29 4 Scalp Tumor Excision Age 32, male, scalp tumor excision, massive bleeding when the tu-mor is excised. Sufficient spraying this powder to the bleeding area, the bleeding stops on contact, after the coagulation is wa-shed away, it is closed by suture.
A-V Fistula Plasty Ase 40, female, acute renal failure, A-V fistula formation opera-tion, massive bleeding. The operation of stopping bleeding consi-sts of combing the powder with pressing with gauzes. When admini-stering this powder to the bleeding area, those that look black in color indicate the black coagulation, while those that are white are the powder that does not get mixed up with the blood yet. At the end of the operation, most of black blood coagulation is wi-ped out with 4x4 gauze, and rinsed with Ringer's solution. It tak-es totally 5 minutes to stop bleeding completely, as the surgeon kept wiping away the coagulation. The patient's conditions are particularly well, better than without using this powder.
Skin Contracture Excision Age 40, male, skin contracture on the palm, which needs to be re-moved, and it requires skin graft. When the skin graft is removed from the hand, massive bleeding occurs. On applying sufficient pow-der to the bleeding area topically, it appears black coagulation on contact. Bleeding stops at the same time as the black coagula-tion forms. Those that appears white indicate the powder not yet get mixed up with the blood. Those that appears more black area indicate the more powder mixed up with the blood. Suture going on.
Paraanal Abscess Excision Age 70, female, paraanal excision, bleeding when it is opened up.
When spraying the powder to the bleeding area, it stops bleeding by forming black blood coagulation on contact. Those that appears white are the powder that are not mixed up with the blood. Suture going on.
[ CA 0209~439 1998-04-29 .
Paraanal Abscess Excision Age 50, male, paraanal abscess excision, massive bleeding when it is opened. On spraying the powder topically to the bleeding area, the black color is formed on contact because of the blood coagula-tion. The white color is the powder instantly not mixed up with the blood yet. Lastly, insert the long gauze into the anus.
Extraction of Teeth Age 30, male, extraction of teeth, gum injected bleeds. Administ-ering this powder topically to the bleeding area, the bleeding sto-ps on contact and black blood coagulation forms at the same time.
Wipe out the black coagulation in 10 seconds, stopped bleeding still persisted.
Extraction of Teeth for Chronic Hepatitis Age 60, female, chronic hepatitis, has bleeding tendency, extrac-tion of teeth causes massive bleeding. Upon applying this powder to the socket of the gum, the black coagulation forms on contact, and the bleeding in the socket stops on contact accordingly.
Finger Scratched Myself, finger little scratched, slightly bleeds. Upon contact with the powder, the black color forms on contact.
Normal, Liver Disease, Colon Cancer and Hemophilia Blood When tested in the tube, 1 milliliter of human blood requires 0.15 68 grams of powdered vitamin C to form black blood coagulation by shaking the tube with hand or stirrer machine. It takes 6 minutes to cause the black blood coagulation unmobile in the test tube for normal, liver diseases, colon cancer and hemophilia blood respec-tively. These experiments have evidenced that the mechanism of action of powdered vitamin C in the formation of black blood coa-gulation does not involve the coagulation factors.
~F
~ CA 0209~439 1998-04-29
Claims (5)
1. A therapeutic instant blood coagulant composition which comprises:
(a) ascorbic acid, or L-threo-hex-2-enono-1,4-lactone, or vitamin C, and mixtures thereof;
(b) excipients.
(a) ascorbic acid, or L-threo-hex-2-enono-1,4-lactone, or vitamin C, and mixtures thereof;
(b) excipients.
2. The composition according to claim 1, wherein the ascorbic acid, or L-threo-hex-2-enono-1,4-lactone, or vitamin C, and excipients are in a powdered form.
3. The composition according to claim 1, wherein the ascorbic acid, or L-threo-hex-2-enono-1,4-lactone, or vitamin C, and excipients are in an aqueous form.
4. The composition according to claim 1, wherein the ascorbic acid, or L-threo-hex-2-enono-1,4-lactone, or vitamin C, and excipients are in a tablet form.
5. The composition according to claim 1, wherein sodium ascorbate is considered vitamin C.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US62409490A | 1990-12-06 | 1990-12-06 | |
US07/624,094 | 1990-12-06 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2095439A1 CA2095439A1 (en) | 1992-06-07 |
CA2095439C true CA2095439C (en) | 1998-12-08 |
Family
ID=24500629
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA 2095439 Expired - Fee Related CA2095439C (en) | 1990-12-06 | 1991-12-05 | Substance that stops any bleeding on contact for medical, surgical and dental uses |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0644754A4 (en) |
AU (1) | AU662505B2 (en) |
CA (1) | CA2095439C (en) |
NO (1) | NO930858D0 (en) |
WO (1) | WO1992010999A1 (en) |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1334933A (en) * | 1971-02-19 | 1973-10-24 | Ahrens G W | Reaction products of caldium ascorbate and preparation containing them |
FR2336925A1 (en) * | 1975-12-30 | 1977-07-29 | Mouney Guy | Dentifrice contg. haemostatic agent, esp. ascorbic acid or salt - has curative action on lesions of gingival epithelium etc. |
JPS6029361B2 (en) * | 1977-03-04 | 1985-07-10 | 白井松新薬株式会社 | Pharmaceutical composition with enhanced hemostatic effect |
US4959362A (en) * | 1983-12-19 | 1990-09-25 | Takeda Chemical Industries, Inc. | Pharmaceutical compositions containing certain ascorbic acid derivatives useful in the prophylaxis and treatment of disorders of the circulatory system |
NO161779C (en) * | 1986-04-22 | 1989-10-04 | Olav Johan Braenden | PROCEDURE FOR PREPARING AN ANTI-COOLING PREPARATION. |
US5021452A (en) * | 1989-01-09 | 1991-06-04 | The Board Of Regents Of The University Of Washington | Process for enhancing wound healing |
US5140043A (en) * | 1989-04-17 | 1992-08-18 | Duke University | Stable ascorbic acid compositions |
-
1991
- 1991-12-05 CA CA 2095439 patent/CA2095439C/en not_active Expired - Fee Related
- 1991-12-05 AU AU91034/91A patent/AU662505B2/en not_active Ceased
- 1991-12-05 EP EP92901379A patent/EP0644754A4/en not_active Withdrawn
- 1991-12-05 WO PCT/US1991/009201 patent/WO1992010999A1/en not_active Application Discontinuation
-
1993
- 1993-03-09 NO NO1993930858A patent/NO930858D0/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU662505B2 (en) | 1995-09-07 |
EP0644754A1 (en) | 1995-03-29 |
EP0644754A4 (en) | 1995-12-27 |
AU9103491A (en) | 1992-07-22 |
NO930858D0 (en) | 1993-03-09 |
CA2095439A1 (en) | 1992-06-07 |
WO1992010999A1 (en) | 1992-07-09 |
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